Is SRCAP p.Pro2951Ala (c.8851C>G) pathogenic?

SRCAP p.Pro2951Ala (c.8851C>G) is classified Benign in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0788); Rare (popmax 0.914%, eas).

How common is SRCAP p.Pro2951Ala (c.8851C>G) in the general population?

SRCAP p.Pro2951Ala (c.8851C>G) is rare (popmax 0.914%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Pro2951Ala (c.8851C>G)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

SRCAP p.Pro2951Ala

c.8851C>G · rs144944402 · VCV318909

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.914%, eas)

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.313	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.39, phastCons 0.94
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	16.89	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.914% East Asian · 410/44,880 alleles

Filtering AF 0.841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.812%

Overall 0.03% 485/1,614,130 alleles · rare exomes 419/1,461,874 · genomes 66/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.914%	109
Remaining individualsnot grpmax-eligible	0.032%	3,126
South Asian	0.0296%	3,373
Middle Eastern	0.0165%	6,062
Admixed American	0.005%	20,002
European (non-Finnish)	0.00203%	49,167

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRCAP
Protein: p.Pro2951Ala
Coding: c.8851C>G
MANE Select: NM_006662
dbSNP: rs144944402
Type: single nucleotide variant
Location: chr16:30738891 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2951: the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

Full SRCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter Pathogenic ★★ same type
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2748Ter Pathogenic ★★ same type
SRCAP p.Gln2407Ter Pathogenic ★★ same type
SRCAP p.Gln2419Ter Pathogenic ★★ same type
SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srcap-p-pro2951ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown