Is SRCAP p.Ala883Gly (c.2648C>G) pathogenic?

SRCAP p.Ala883Gly (c.2648C>G) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-20). AlphaMissense: ambiguous (0.3949); Ultra-rare (popmax 0.0627%, afr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Ala883Gly (c.2648C>G) in the general population?

SRCAP p.Ala883Gly (c.2648C>G) is ultra-rare (popmax 0.0627%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ala883Gly (c.2648C>G)?

AlphaMissense predicts ambiguous (score 0.3949) — an in-silico prediction, not a clinical call.

SRCAP p.Ala883Gly

Q: What condition is associated with SRCAP p.Ala883Gly (c.2648C>G)?

SRCAP p.Ala883Gly (c.2648C>G) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.2648C>G · rs139524110 · VCV1441746

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, afr)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.3949	ambiguous
REVEL	0.485	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · 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 0.0627% African / African-American · 47/74,912 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00304% 49/1,614,028 alleles · ultra-rare exomes 23/1,461,874 · genomes 26/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0627%	1,594
Admixed American	0.00333%	29,998

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.Ala883Gly
Coding: c.2648C>G
MANE Select: NM_006662
dbSNP: rs139524110
Type: single nucleotide variant
Location: chr16:30716310 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 883: an α-helix; a UniProt-annotated variant site (in dehmba)

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

Disease context

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome

Similar variants

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
SRCAP p.Gln2665Ter Pathogenic/Likely 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-ala883gly (accessed [today's date]).

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