Is SRCAP p.Ser3050Arg (c.9150T>A) pathogenic?

SRCAP p.Ser3050Arg (c.9150T>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-05). AlphaMissense: likely pathogenic (0.6509); Very rare (popmax 0.00267%, afr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Ser3050Arg (c.9150T>A)?

SRCAP p.Ser3050Arg (c.9150T>A) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Ser3050Arg (c.9150T>A) in the general population?

SRCAP p.Ser3050Arg (c.9150T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ser3050Arg (c.9150T>A)?

AlphaMissense predicts likely pathogenic (score 0.6509) — an in-silico prediction, not a clinical call.

SRCAP p.Ser3050Arg

c.9150T>A · rs557654038 · VCV2164265

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.6509	likely pathogenic
REVEL	0.405	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	21.0	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 0.00267% African / African-American · 2/74,806 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00093% 15/1,613,184 alleles · very rare exomes 13/1,461,498 · genomes 2/151,686 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,403
South Asian	0.0022%	45,523
European (non-Finnish)	0.000932%	107,261

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.Ser3050Arg
Coding: c.9150T>A
MANE Select: NM_006662
dbSNP: rs557654038
Type: single nucleotide variant
Location: chr16:30739190 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3050: 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.Ser3050= Likely benign ★ 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-ser3050arg (accessed [today's date]).

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