Is SRCAP p.Arg2737= (c.8209C>A) pathogenic?

SRCAP p.Arg2737= (c.8209C>A) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-25). Ultra-rare (popmax 0.0401%, eas); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Arg2737= (c.8209C>A) in the general population?

SRCAP p.Arg2737= (c.8209C>A) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

SRCAP p.Arg2737=

Q: What condition is associated with SRCAP p.Arg2737= (c.8209C>A)?

SRCAP p.Arg2737= (c.8209C>A) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.8209C>A · rs770652502 · VCV2969987

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

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 0.64	GERP -3.2, phastCons 0.89
Overall
CADD	5.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,878 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00155% 25/1,612,934 alleles · ultra-rare exomes 20/1,460,598 · genomes 5/152,336 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,493
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.000509%	196,547

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.Arg2737=
Coding: c.8209C>A
MANE Select: NM_006662
dbSNP: rs770652502
Type: single nucleotide variant
Location: chr16:30738249 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2737: 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.Arg2737Gln Uncertain significance ★★ ⚠ same residue
SRCAP p.Arg2737Gly Uncertain significance ★★ ⚠ same residue
SRCAP p.Arg2737Trp 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

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-arg2737 (accessed [today's date]).

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