# NM_001384125.1(BLTP1):c.11396T>C (p.Phe3799Ser)

https://sugi.bio/variant/bltp1-p-phe3799ser

## Summary

**BLTP1 p.Phe3799Ser (c.11396T>C)** is classified **Uncertain significance** in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.1978); Absent from gnomAD v4.1; Associated with BLTP1-related disorder.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs2482740668 · 1 submitter · 1 linked condition · AlphaMissense likely benign · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the BLTP1 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter, and is linked to BLTP1-related disorder.

*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 | [BLTP1](https://sugi.bio/atlas/gene/BLTP1/) |
| Protein change (HGVS p.) | p.Phe3799Ser |
| Coding change (HGVS c.) | c.11396T>C |
| MANE Select transcript | [NM_001384125](https://www.ncbi.nlm.nih.gov/nuccore/NM_001384125) |
| dbSNP | [rs2482740668](https://www.ncbi.nlm.nih.gov/snp/rs2482740668/) |
| Variant type | single nucleotide variant |
| Location | chr4:122328240-122328240 (GRCh38) |
| ClinVar | [VCV2629793](https://www.ncbi.nlm.nih.gov/clinvar/variation/2629793/) |

**All HGVS expressions:** `NC_000004.11:g.123249395T>C`, `NC_000004.12:g.122328240T>C`, `NG_015813.2:g.162638T>C`, `NG_015813.3:g.180911T>C`, `NM_001384125.1:c.11396T>C`, `NM_015312.4:c.11132T>C`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.1978)
- REVEL 0.503 (indeterminate)
- Conservation: phyloP 6.134, GERP 1.75, phastCons 1 — highly conserved (differs from AlphaMissense)
- ⚠ **Isoform check:** AlphaMissense is numbered on a different transcript (AM **F3711S** vs ClinVar **F3799S**) — the AlphaMissense read here may be for a different residue; verify against the ClinVar transcript.
- CADD: **PHRED 20.4**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 0.84** across the covering region of the MANE Select transcript (122,324,437–122,336,195), spanning 11,758 bp. Chi-square p 0.0011. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*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}


Curated gene–disease validity (ClinGen):

- **Alkuraya-Kucinskas syndrome** — Definitive (AR)

## Protein context {#protein}

Residue **3799** lies in a UniProt-annotated variant site (in alkkucs).

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-12-27.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-12-27 |

## Associated conditions {#conditions}

[BLTP1-related disorder](https://sugi.bio/atlas/disease/bltp1-related-disorder/).

**Reported phenotype names (ClinVar):** BLTP1-related disorder, BLTP1-related condition.

## Similar variants {#similar}

Related BLTP1 variant pages (same residue, condition, or type): [BLTP1 p.Arg968Cys](/variant/bltp1-p-arg968cys), [BLTP1 p.His3063Arg](/variant/bltp1-p-his3063arg), [BLTP1 c.10312+2T>C](/variant/bltp1-c-10312-plus-2t-c), [BLTP1 c.11513+1G>C](/variant/bltp1-c-11513-plus-1g-c), [BLTP1 c.5184+1G>T](/variant/bltp1-c-5184-plus-1g-t), [BLTP1 p.Arg3190Ter](/variant/bltp1-p-arg3190ter), [BLTP1 p.Val1878Ala](/variant/bltp1-p-val1878ala), [BLTP1 c.6378+10T>C](/variant/bltp1-c-6378-plus-10t-c).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 2629793). 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.*