Is SRCAP p.Gly23Ser (c.67G>A) pathogenic?

SRCAP p.Gly23Ser (c.67G>A) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.0672); Rare (popmax 0.236%, eas).

How common is SRCAP p.Gly23Ser (c.67G>A) in the general population?

SRCAP p.Gly23Ser (c.67G>A) is rare (popmax 0.236%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Gly23Ser (c.67G>A)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

SRCAP p.Gly23Ser

c.67G>A · rs138333984 · VCV1532725

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.236%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.207	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 5.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,462 bp · p 0.64 · regional, not allelic
Overall
CADD	23.6	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 0.236% East Asian · 106/44,868 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.00694% 112/1,613,074 alleles · rare exomes 100/1,460,840 · genomes 12/152,234 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.236%	423
Admixed American	0.00167%	59,882
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000339%	294,841

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.Gly23Ser
Coding: c.67G>A
MANE Select: NM_006662
dbSNP: rs138333984
Type: single nucleotide variant
Location: chr16:30704076 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 23: the 'disordered' region

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

Similar variants

SRCAP p.Gly23Arg 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-gly23ser (accessed [today's date]).

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