Is SRCAP p.Gln2770del (c.8306AGC[1]) pathogenic?

SRCAP p.Gln2770del (c.8306AGC[1]) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0231%, afr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Gln2770del (c.8306AGC[1]) in the general population?

SRCAP p.Gln2770del (c.8306AGC[1]) is ultra-rare (popmax 0.0231%, afr) (gnomAD).

SRCAP p.Gln2770del

Q: What condition is associated with SRCAP p.Gln2770del (c.8306AGC[1])?

SRCAP p.Gln2770del (c.8306AGC[1]) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.8306AGC[1] · VCV3580232

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, 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 · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	16.12	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GCG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% African / African-American · 17/73,746 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.00115% 18/1,570,940 alleles · ultra-rare exomes 7/1,418,626 · genomes 11/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0231%	4,338
European (non-Finnish)	8.63e-05%	1,158,460

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.Gln2770del
Coding: c.8306AGC[1]
MANE Select: NM_006662
Type: Microsatellite
Location: chr16:30738344 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2770: 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.Glu3182del 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-gln2770del (accessed [today's date]).

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