Is SRCAP p.Arg2965Gln (c.8894G>A) pathogenic?

SRCAP p.Arg2965Gln (c.8894G>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-27). AlphaMissense: likely benign (0.1215); Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

How common is SRCAP p.Arg2965Gln (c.8894G>A) in the general population?

SRCAP p.Arg2965Gln (c.8894G>A) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Arg2965Gln (c.8894G>A)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2965Gln

Q: What condition is associated with SRCAP p.Arg2965Gln (c.8894G>A)?

SRCAP p.Arg2965Gln (c.8894G>A) is associated with Inborn genetic diseases, Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

c.8894G>A · rs201043719 · VCV2958726

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.478	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · 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 0.0217% Admixed American · 13/59,994 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00161% 26/1,613,944 alleles · ultra-rare exomes 19/1,461,746 · genomes 7/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,615
East Asian	0.00892%	11,217
African / African-American	0.004%	24,997
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.000424%	235,992

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.Arg2965Gln
Coding: c.8894G>A
MANE Select: NM_006662
dbSNP: rs201043719
Type: single nucleotide variant
Location: chr16:30738934 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2965: the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Arg2965Trp Benign/Likely benign ★★ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Gln2419Ter Pathogenic ★★ 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-arg2965gln (accessed [today's date]).

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