Is SRCAP p.Glu95Lys (c.283G>A) pathogenic?

SRCAP p.Glu95Lys (c.283G>A) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-07). AlphaMissense: likely pathogenic (0.8494); Very rare (popmax 0.00223%, eas); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Glu95Lys (c.283G>A) in the general population?

SRCAP p.Glu95Lys (c.283G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Glu95Lys (c.283G>A)?

AlphaMissense predicts likely pathogenic (score 0.8494) — an in-silico prediction, not a clinical call.

SRCAP p.Glu95Lys

Q: What condition is associated with SRCAP p.Glu95Lys (c.283G>A)?

SRCAP p.Glu95Lys (c.283G>A) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.283G>A · VCV3580056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.8494	likely pathogenic
REVEL	0.322	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,369 bp · p 5.9e-15 · regional, not allelic
Overall
CADD	25.3	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 0.00223% East Asian · 1/44,844 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,611,818 alleles · very rare exomes 5/1,459,592 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,844
South Asian	0.0011%	90,908
European (non-Finnish)	0.000339%	294,619

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.Glu95Lys
Coding: c.283G>A
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30704292 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 95: an α-helix

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-glu95lys (accessed [today's date]).

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