Is SRCAP p.Glu1902Gln (c.5704G>C) pathogenic?

SRCAP p.Glu1902Gln (c.5704G>C) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-15). AlphaMissense: likely benign (0.254); Very rare (popmax 0.00267%, afr).

How common is SRCAP p.Glu1902Gln (c.5704G>C) in the general population?

SRCAP p.Glu1902Gln (c.5704G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Glu1902Gln (c.5704G>C)?

AlphaMissense predicts likely benign (score 0.254) — an in-silico prediction, not a clinical call.

SRCAP p.Glu1902Gln

c.5704G>C · rs1019525148 · VCV1311128

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.254	likely benign
REVEL	0.357	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.4	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 0.00267% African / African-American · 2/74,902 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,614,014 alleles · very rare exomes 7/1,461,862 · genomes 2/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,451
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000424%	236,007

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.Glu1902Gln
Coding: c.5704G>C
MANE Select: NM_006662
dbSNP: rs1019525148
Type: single nucleotide variant
Location: chr16:30729011 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1902: an α-helix; 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.Glu1902Gly Benign/Likely benign ★★ same residue
SRCAP p.Glu1902Lys 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-glu1902gln (accessed [today's date]).

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