Is SRCAP p.Ser1033Pro (c.3097T>C) pathogenic?

SRCAP p.Ser1033Pro (c.3097T>C) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-13). AlphaMissense: likely benign (0.063); Rare (popmax 0.858%, amr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Ser1033Pro (c.3097T>C)?

SRCAP p.Ser1033Pro (c.3097T>C) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Ser1033Pro (c.3097T>C) in the general population?

SRCAP p.Ser1033Pro (c.3097T>C) is rare (popmax 0.858%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Ser1033Pro (c.3097T>C)?

AlphaMissense predicts likely benign (score 0.063) — an in-silico prediction, not a clinical call.

SRCAP p.Ser1033Pro

c.3097T>C · rs202000509 · VCV318872

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.063 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.858%, amr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.063	likely benign
REVEL	0.301	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 1.7, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	17.06	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 0.858% Admixed American · 515/60,018 alleles

Filtering AF 0.797% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.773%

Overall 0.0354% 572/1,614,106 alleles · rare exomes 381/1,461,846 · genomes 191/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.858%	117
Remaining individualsnot grpmax-eligible	0.0672%	1,488
African / African-American	0.0147%	6,821
East Asian	0.00446%	22,439
European (non-Finnish)	0.000169%	589,998

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.Ser1033Pro
Coding: c.3097T>C
MANE Select: NM_006662
dbSNP: rs202000509
Type: single nucleotide variant
Location: chr16:30720822 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1033: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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.Ser1033Leu 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-ser1033pro (accessed [today's date]).

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