Is SRCAP p.Arg337Cys (c.1009C>T) pathogenic?

SRCAP p.Arg337Cys (c.1009C>T) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.114); Very rare (popmax 0.00314%, nfe).

How common is SRCAP p.Arg337Cys (c.1009C>T) in the general population?

SRCAP p.Arg337Cys (c.1009C>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Arg337Cys (c.1009C>T)?

AlphaMissense predicts likely benign (score 0.114) — an in-silico prediction, not a clinical call.

SRCAP p.Arg337Cys

c.1009C>T · rs376483582 · VCV2177012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Computational evidence

Protein change
AlphaMissense	0.114	likely benign
REVEL	0.528	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 127 bp · p 0.0011 · regional, not allelic
Overall
CADD	27.8	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 0.00314% European (non-Finnish) · 37/1,180,022 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00242% 39/1,614,146 alleles · very rare exomes 39/1,461,890 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,082

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.Arg337Cys
Coding: c.1009C>T
MANE Select: NM_006662
dbSNP: rs376483582
Type: single nucleotide variant
Location: chr16:30710003 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 337: the 'disordered' region

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

Similar variants

SRCAP p.Arg337Leu Uncertain significance ★ same residue
SRCAP p.Arg337Ser Uncertain significance ★ 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

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-arg337cys (accessed [today's date]).

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