Is SRCAP p.Ala540Val (c.1619C>T) pathogenic?

SRCAP p.Ala540Val (c.1619C>T) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0929); Rare (popmax 0.123%, amr).

How common is SRCAP p.Ala540Val (c.1619C>T) in the general population?

SRCAP p.Ala540Val (c.1619C>T) is rare (popmax 0.123%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Ala540Val (c.1619C>T)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

SRCAP p.Ala540Val

c.1619C>T · rs746443116 · VCV788681

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.087	GERP -1.9, phastCons 0.009
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	17.04	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 0.123% Admixed American · 74/59,968 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0924%

Overall 0.00465% 75/1,613,794 alleles · rare exomes 73/1,461,870 · genomes 2/151,924 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.123%	810
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ala540Val
Coding: c.1619C>T
MANE Select: NM_006662
dbSNP: rs746443116
Type: single nucleotide variant
Location: chr16:30711961 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 540: a UniProt-annotated variant site (in dehmba); the 'disordered' region

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

Similar variants

SRCAP p.Ala540= Likely benign ★ same residue
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

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-ala540val (accessed [today's date]).

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