Is SRCAP p.Ser2955= (c.8865C>G) pathogenic?

SRCAP p.Ser2955= (c.8865C>G) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.819%, afr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Ser2955= (c.8865C>G)?

SRCAP p.Ser2955= (c.8865C>G) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Ser2955= (c.8865C>G) in the general population?

SRCAP p.Ser2955= (c.8865C>G) is rare (popmax 0.819%, afr) (gnomAD).

SRCAP p.Ser2955=

c.8865C>G · rs149043190 · VCV318910

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.819%, afr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -4.9, phastCons 0.93
Overall
CADD	2.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.819% African / African-American · 615/75,050 alleles

Filtering AF 0.766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.0437% 706/1,614,178 alleles · rare exomes 347/1,461,874 · genomes 359/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.819%	122
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Middle Eastern	0.0495%	2,021
Admixed American	0.0433%	2,308
South Asian	0.0011%	91,084
European (non-Finnish)	0.000763%	131,114

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.Ser2955=
Coding: c.8865C>G
MANE Select: NM_006662
dbSNP: rs149043190
Type: single nucleotide variant
Location: chr16:30738905 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2955: 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.Ser2955Ala Uncertain significance ★ ⚠ same residue
SRCAP p.Ser2955Phe 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

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-ser2955 (accessed [today's date]).

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