Is SRCAP p.Arg3065Cys (c.9193C>T) pathogenic?

SRCAP p.Arg3065Cys (c.9193C>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.7798); Ultra-rare (popmax 0.0233%, amr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg3065Cys (c.9193C>T)?

SRCAP p.Arg3065Cys (c.9193C>T) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Arg3065Cys (c.9193C>T) in the general population?

SRCAP p.Arg3065Cys (c.9193C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Arg3065Cys (c.9193C>T)?

AlphaMissense predicts likely pathogenic (score 0.7798) — an in-silico prediction, not a clinical call.

SRCAP p.Arg3065Cys

c.9193C>T · rs760273993 · VCV1488164

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.7798	likely pathogenic
REVEL	0.57	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	28.9	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 0.0233% Admixed American · 14/60,000 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.000992% 16/1,613,310 alleles · ultra-rare exomes 14/1,461,100 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
European (non-Finnish)	0.000169%	590,005

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.Arg3065Cys
Coding: c.9193C>T
MANE Select: NM_006662
dbSNP: rs760273993
Type: single nucleotide variant
Location: chr16:30739233 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3065: 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-arg3065cys (accessed [today's date]).

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