Is SRCAP p.Arg1957Gln (c.5870G>A) pathogenic?

SRCAP p.Arg1957Gln (c.5870G>A) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-30). AlphaMissense: likely benign (0.0532); Rare (popmax 0.234%, sas).

How common is SRCAP p.Arg1957Gln (c.5870G>A) in the general population?

SRCAP p.Arg1957Gln (c.5870G>A) is rare (popmax 0.234%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Arg1957Gln (c.5870G>A)?

AlphaMissense predicts likely benign (score 0.0532) — an in-silico prediction, not a clinical call.

SRCAP p.Arg1957Gln

c.5870G>A · rs139158885 · VCV2155210

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0532 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0532	likely benign
REVEL	0.276	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 -0.44	GERP -5.2, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	9.639	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 0.234% South Asian · 213/91,060 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.0172% 278/1,613,658 alleles · rare exomes 262/1,461,438 · genomes 16/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.234%	428
Remaining individualsnot grpmax-eligible	0.0304%	3,289
East Asian	0.0156%	6,411
Admixed American	0.00667%	14,997
European (non-Finnish)	0.00297%	33,706

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.Arg1957Gln
Coding: c.5870G>A
MANE Select: NM_006662
dbSNP: rs139158885
Type: single nucleotide variant
Location: chr16:30729177 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1957: a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Arg1957Gly 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
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-arg1957gln (accessed [today's date]).

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