Is SRCAP p.Glu3182del (c.9537GGA[2]) pathogenic?

SRCAP p.Glu3182del (c.9537GGA[2]) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-28). Ultra-rare (popmax 0.0135%, eas); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Glu3182del (c.9537GGA[2]) in the general population?

SRCAP p.Glu3182del (c.9537GGA[2]) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

SRCAP p.Glu3182del

Q: What condition is associated with SRCAP p.Glu3182del (c.9537GGA[2])?

SRCAP p.Glu3182del (c.9537GGA[2]) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.9537GGA[2] · rs376601598 · VCV1394390

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, 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 · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -3.2, phastCons 0.98
Overall
CADD	18.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% East Asian · 6/44,402 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.00118% 19/1,605,816 alleles · ultra-rare exomes 16/1,453,634 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0135%	7,400
Admixed American	0.00342%	29,274
Remaining individualsnot grpmax-eligible	0.00322%	31,052
Finnishnot grpmax-eligible	0.00319%	31,394
South Asian	0.00111%	90,386
European (non-Finnish)	0.00051%	196,095

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.Glu3182del
Coding: c.9537GGA[2]
MANE Select: NM_006662
dbSNP: rs376601598
Type: Microsatellite
Location: chr16:30739575 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3182: 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.Gln2770del Uncertain significance ★★ same condition
SRCAP p.Pro2488del Uncertain significance ★★ same condition
SRCAP p.Ser2576del Uncertain significance ★★ same condition
SRCAP p.Glu2405fs Pathogenic ★ same condition
SRCAP p.Val2646fs Likely pathogenic ★ same condition
SRCAP p.Arg2768_Gln2769insArg Uncertain significance ★ same condition
SRCAP p.Asp548del Uncertain significance ★ same condition
SRCAP p.Glu3181_Glu3182del Uncertain significance ★ 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-glu3182del (accessed [today's date]).

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