# NM_006662.3(SRCAP):c.3024_3026del (p.Val1012del)

https://sugi.bio/variant/srcap-p-val1012del

## Summary

**SRCAP p.Val1012del (c.3024_3026del)** is classified **Uncertain significance** in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-29). Very rare (popmax 0.004%, afr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

**At a glance:** Uncertain significance · review: Multiple submitters · rsID rs754762497 · 3 submitters · 2 linked conditions · very rare (popmax 0.004%, afr)

## For patients & families {#patients}

This is a change in the SRCAP gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 3 submitters, and is linked to developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [SRCAP](https://sugi.bio/atlas/gene/SRCAP/) |
| Protein change (HGVS p.) | p.Val1012del |
| Coding change (HGVS c.) | c.3024_3026del |
| MANE Select transcript | [NM_006662](https://www.ncbi.nlm.nih.gov/nuccore/NM_006662) |
| dbSNP | [rs754762497](https://www.ncbi.nlm.nih.gov/snp/rs754762497/) |
| Variant type | Deletion |
| Location | chr16:30720749-30720751 (GRCh38) |
| ClinVar | [VCV1981702](https://www.ncbi.nlm.nih.gov/clinvar/variation/1981702/) |

**All HGVS expressions:** `NC_000016.10:g.30720749_30720751del`, `NC_000016.9:g.30732070_30732072del`, `NG_032135.1:g.26609_26611del`, `NG_032135.2:g.26580_26582del`, `NM_006662.3:c.3024_3026del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 7.736, GERP 2.74, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **in-frame indel**.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.004%** (afr) · FAF95 0.00106% · FAF99 0.000495% · 3/74,992 in the highest group · 8/1,612,188 alleles overall — very rare (popmax 0.004%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.004% | 24,997 |
| East Asian | 0.00223% | 44,860 |
| European (non-Finnish) | 0.000339% | 294,745 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**SRCAP** population constraint: LOEUF 0.223, pLI 1, missense-Z 3.6475; ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Floating-Harbor syndrome** — Definitive (AD)

## Protein context {#protein}

Residue **1012** lies in a UniProt-annotated variant site (in dehmba).

**22 experimental structure(s)** (PDB): [6IGM](https://www.rcsb.org/structure/6IGM), [8X15](https://www.rcsb.org/structure/8X15), [8X19](https://www.rcsb.org/structure/8X19), [8X1C](https://www.rcsb.org/structure/8X1C), [9CA7](https://www.rcsb.org/structure/9CA7), [9CA8](https://www.rcsb.org/structure/9CA8) — incl. mutant structure 9UBD.

## What this gene does {#gene-function}

*Describes the biological roles of SRCAP (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** SRCAP's established molecular role includes transcription coactivator activity.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** transcription coactivator activity, ATP-dependent chromatin remodeler activity.

**Biological process:** positive regulation of transcription by RNA polymerase II, cAMP/PKA signal transduction.

## Clinical significance {#significance}

**Uncertain significance** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-10-29.

**Submitter consensus:** unanimous (3/3 Uncertain significance).

**Submission history:** 3 submissions (2023–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-05-01 |
| Revvity Omics, Revvity | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-09-26 |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2025-10-29 |

## Associated conditions {#conditions}

[developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities](https://sugi.bio/atlas/disease/developmental-delay-hypotonia-musculoskeletal-defects-and-behavioral-abnormalities/), [Floating-Harbor syndrome](https://sugi.bio/atlas/disease/floating-harbor-syndrome/).

**Reported phenotype names (ClinVar):** Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, not provided, Floating-Harbor syndrome, SRCAP-Related Floating-Harbor Syndrome, Short stature with delayed bone age, expressive language delay, a triangular face with a prominent nose and deep-set eyes, Pelletier-Leisti syndrome, none provided.

## Similar variants {#similar}

Related SRCAP variant pages (same residue, condition, or type): [SRCAP p.Pro2459fs](/variant/srcap-p-pro2459fs), [SRCAP p.Pro2461fs](/variant/srcap-p-pro2461fs), [SRCAP c.1187_1228+67del](/variant/srcap-c-1187-1228-plus-67del), [SRCAP c.1319del](/variant/srcap-c-1319del), [SRCAP c.2298_2300+3del](/variant/srcap-c-2298-2300-plus-3del), [SRCAP p.Ala2262fs](/variant/srcap-p-ala2262fs), [SRCAP p.Arg1897fs](/variant/srcap-p-arg1897fs), [SRCAP p.Gln2517fs](/variant/srcap-p-gln2517fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1981702). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*