Is SRCAP p.Arg3188Cys (c.9562C>T) pathogenic?

SRCAP p.Arg3188Cys (c.9562C>T) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.148); Rare (popmax 0.132%, afr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg3188Cys (c.9562C>T)?

SRCAP p.Arg3188Cys (c.9562C>T) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Arg3188Cys (c.9562C>T) in the general population?

SRCAP p.Arg3188Cys (c.9562C>T) is rare (popmax 0.132%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Arg3188Cys (c.9562C>T)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

SRCAP p.Arg3188Cys

c.9562C>T · rs201133838 · VCV1551169

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, afr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.372	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	25.5	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 0.132% African / African-American · 98/74,514 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.00871% 139/1,595,204 alleles · rare exomes 84/1,442,826 · genomes 55/152,378 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.132%	760
Admixed American	0.0247%	4,055
Remaining individualsnot grpmax-eligible	0.00973%	10,282
European (non-Finnish)	0.00171%	58,585
South Asian	0.00112%	89,336

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.Arg3188Cys
Coding: c.9562C>T
MANE Select: NM_006662
dbSNP: rs201133838
Type: single nucleotide variant
Location: chr16:30739602 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3188: 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.Arg3188His Uncertain significance ★★ ⚠ 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-arg3188cys (accessed [today's date]).

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