Is SRCAP p.Gly2839Ser (c.8515G>A) pathogenic?

SRCAP p.Gly2839Ser (c.8515G>A) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0723); Rare (popmax 0.108%, afr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Gly2839Ser (c.8515G>A)?

SRCAP p.Gly2839Ser (c.8515G>A) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Gly2839Ser (c.8515G>A) in the general population?

SRCAP p.Gly2839Ser (c.8515G>A) is rare (popmax 0.108%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Gly2839Ser (c.8515G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

SRCAP p.Gly2839Ser

c.8515G>A · rs139886717 · VCV318906

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.271	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -4.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	8.841	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 0.108% African / African-American · 81/74,900 alleles

Filtering AF 0.0891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0821%

Overall 0.00596% 96/1,611,332 alleles · rare exomes 45/1,459,040 · genomes 51/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	925
Admixed American	0.0151%	6,610
Remaining individualsnot grpmax-eligible	0.00962%	10,393

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.Gly2839Ser
Coding: c.8515G>A
MANE Select: NM_006662
dbSNP: rs139886717
Type: single nucleotide variant
Location: chr16:30738555 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2839: 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

Floating-Harbor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

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-gly2839ser (accessed [today's date]).

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