Is SRCAP p.Glu222Gln (c.664G>C) pathogenic?

SRCAP p.Glu222Gln (c.664G>C) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-09). AlphaMissense: likely pathogenic (0.7634); Very rare (popmax 8.47e-05%, nfe); Associated with SRCAP-related disorder.

What condition is associated with SRCAP p.Glu222Gln (c.664G>C)?

SRCAP p.Glu222Gln (c.664G>C) is associated with SRCAP-related disorder (ClinVar).

How common is SRCAP p.Glu222Gln (c.664G>C) in the general population?

SRCAP p.Glu222Gln (c.664G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Glu222Gln (c.664G>C)?

AlphaMissense predicts likely pathogenic (score 0.7634) — an in-silico prediction, not a clinical call.

SRCAP p.Glu222Gln

c.664G>C · rs1385467684 · VCV2636593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

SRCAP-related disorder

Computational evidence

Protein change
AlphaMissense	0.7634	likely pathogenic
REVEL	0.621	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,369 bp · p 5.9e-15 · regional, not allelic
Overall
CADD	24.5	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.2e-05% 1/1,614,190 alleles · very rare exomes 1/1,461,890 · genomes 0/152,300 · joint denominator

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.Glu222Gln
Coding: c.664G>C
MANE Select: NM_006662
dbSNP: rs1385467684
Type: single nucleotide variant
Location: chr16:30709543 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 222: an α-helix

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

Disease context

SRCAP-related disorder

Similar variants

SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln3043His Uncertain significance ★★ ⚠ same condition
SRCAP p.Gln3202His Uncertain significance ★★ same condition
SRCAP p.Leu2652Arg Uncertain significance ★★ same condition
SRCAP p.Pro1728Ala Uncertain significance ★★ ⚠ same condition
SRCAP p.Thr1745Met Uncertain significance ★★ ⚠ same condition

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-glu222gln (accessed [today's date]).

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