Is SRCAP p.Arg3077= (c.9229C>A) pathogenic?

SRCAP p.Arg3077= (c.9229C>A) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-11). Rare (popmax 0.841%, mid); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg3077= (c.9229C>A)?

SRCAP p.Arg3077= (c.9229C>A) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Arg3077= (c.9229C>A) in the general population?

SRCAP p.Arg3077= (c.9229C>A) is rare (popmax 0.841%, mid) (gnomAD).

SRCAP p.Arg3077=

c.9229C>A · rs143133981 · VCV318918

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.841%, mid)

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 1.5	GERP 0.45, phastCons 0.8
Overall
CADD	4.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.841% Middle Eastern · 51/6,062 alleles

Filtering AF 0.657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.592%

Overall 0.0734% 1,184/1,613,936 alleles · rare exomes 1,073/1,461,628 · genomes 111/152,308 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.841%	119
Ashkenazi Jewishnot grpmax-eligible	0.571%	175
South Asian	0.386%	259
Remaining individualsnot grpmax-eligible	0.154%	651
Admixed American	0.08%	1,251
Finnishnot grpmax-eligible	0.0455%	2,199
European (non-Finnish)	0.0364%	2,744
East Asian	0.00891%	11,220
African / African-American	0.00666%	15,012

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.Arg3077=
Coding: c.9229C>A
MANE Select: NM_006662
dbSNP: rs143133981
Type: single nucleotide variant
Location: chr16:30739269 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3077: 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.Arg3077Ter Likely pathogenic ★ same residue
SRCAP p.Arg3077Gln 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-arg3077 (accessed [today's date]).

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