# NM_144668.6(CFAP251):c.1533T>C (p.Asp511=)

https://sugi.bio/variant/cfap251-p-asp511

## Summary

**CFAP251 p.Asp511= (c.1533T>C)** is classified **Likely benign** in CFAP251 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Rare (popmax 0.595%, sas); Associated with CFAP251-related disorder.

**At a glance:** Likely benign · review: No assertion criteria · rsID rs576781184 · 1 submitter · 1 linked condition · rare (popmax 0.595%, sas)

## For patients & families {#patients}

This is a change in the CFAP251 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to CFAP251-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 | [CFAP251](https://sugi.bio/atlas/gene/CFAP251/) |
| Protein change (HGVS p.) | p.Asp511= |
| Coding change (HGVS c.) | c.1533T>C |
| MANE Select transcript | [NM_144668](https://www.ncbi.nlm.nih.gov/nuccore/NM_144668) |
| dbSNP | [rs576781184](https://www.ncbi.nlm.nih.gov/snp/rs576781184/) |
| Variant type | single nucleotide variant |
| Location | chr12:121954332-121954332 (GRCh38) |
| ClinVar | [VCV3042607](https://www.ncbi.nlm.nih.gov/clinvar/variation/3042607/) |

**All HGVS expressions:** `NC_000012.11:g.122392238T>C`, `NC_000012.12:g.121954332T>C`, `NG_021364.2:g.40776T>C`, `NM_001178003.2:c.1533T>C`, `NM_144668.6:c.1533T>C`

## 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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.55) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -2.029, GERP -3.64 — fast-evolving / accelerated position
- CADD: **PHRED 1.946**. 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.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.01**, donor gain **0.55**. Largest is donor gain, 2 bp away.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.01**, donor gain **0.00**.
  Masked SpliceAI — what Ensembl VEP and the Broad lookup serve by default — is below the reporting threshold here, so those tools show **no splice signal** for this allele. Masking zeroes a loss scored against a position that is not an annotated splice site, and a gain that merely strengthens an existing one, so the raw score above is describing a cryptic site rather than the site the variant sits on. *No ACMG code is assigned either way.*
- Population frequency (gnomAD v4.1): grpmax **0.595%** (sas) · FAF95 0.553% · FAF99 0.537% · 528/88,678 in the highest group · 554/1,601,764 alleles overall — rare (popmax 0.595%, sas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| South Asian (grpmax) | 0.595% | 168 |
| Remaining individuals (not grpmax-eligible) | 0.0371% | 2,699 |
| Middle Eastern | 0.0341% | 2,936 |
| European (non-Finnish) | 8.52e-05% | 1,174,064 |

*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}

**CFAP251** population constraint: LOEUF 0.829, pLI 5.7652e-19, missense-Z 1.6369. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **511** lies in a UniProt-annotated variant site (in spgf33).

AlphaFold model confidence (whole protein): pLDDT 76.84, 50% of residues very-high.

**1 experimental structure(s)** (PDB): [8J07](https://www.rcsb.org/structure/8J07).

## Clinical significance {#significance}

**Likely benign** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2019-07-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2019-07-01 |

## Associated conditions {#conditions}

[CFAP251-related disorder](https://sugi.bio/atlas/disease/cfap251-related-disorder/).

**Reported phenotype names (ClinVar):** CFAP251-related disorder, CFAP251-related condition.

## Similar variants {#similar}

Related CFAP251 variant pages (same residue, condition, or type): [CFAP251 p.Arg267Ter](/variant/cfap251-p-arg267ter), [CFAP251 c.2492+10C>G](/variant/cfap251-c-2492-plus-10c-g), [CFAP251 p.Asn286=](/variant/cfap251-p-asn286), [CFAP251 p.Glu207=](/variant/cfap251-p-glu207), [CFAP251 p.Gly649=](/variant/cfap251-p-gly649), [CFAP251 p.His356=](/variant/cfap251-p-his356), [CFAP251 p.His740=](/variant/cfap251-p-his740), [CFAP251 p.Leu445Phe](/variant/cfap251-p-leu445phe).

### 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 3042607). 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.*