Is SRCAP p.Pro2791= (c.8373G>A) pathogenic?

SRCAP p.Pro2791= (c.8373G>A) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-27). Ultra-rare (popmax 0.0728%, afr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Pro2791= (c.8373G>A) in the general population?

SRCAP p.Pro2791= (c.8373G>A) is ultra-rare (popmax 0.0728%, afr) (gnomAD).

SRCAP p.Pro2791=

Q: What condition is associated with SRCAP p.Pro2791= (c.8373G>A)?

SRCAP p.Pro2791= (c.8373G>A) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.8373G>A · rs150187491 · VCV1659633

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0728%, afr)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

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 0.26	GERP -4.8, phastCons 0.41
Overall
CADD	2.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0728% African / African-American · 53/72,808 alleles

Filtering AF 0.0571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0516%

Overall 0.0247% 383/1,547,638 alleles · ultra-rare exomes 339/1,395,342 · genomes 44/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0728%	1,374
Middle Eastern	0.0349%	2,868
European (non-Finnish)	0.0269%	3,714
Remaining individualsnot grpmax-eligible	0.0168%	5,953
Admixed American	0.00996%	10,041
South Asian	0.00499%	20,021

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.Pro2791=
Coding: c.8373G>A
MANE Select: NM_006662
dbSNP: rs150187491
Type: single nucleotide variant
Location: chr16:30738413 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2791: 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

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome

Similar variants

SRCAP p.Pro2791Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro2791 (accessed [today's date]).

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