Is SRCAP p.Ser2576del (c.7722CTC[1]) pathogenic?

SRCAP p.Ser2576del (c.7722CTC[1]) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-27). Very rare (popmax 0.00678%, nfe); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Ser2576del (c.7722CTC[1]) in the general population?

SRCAP p.Ser2576del (c.7722CTC[1]) is very rare (popmax 0.00678%, nfe) (gnomAD).

SRCAP p.Ser2576del

Q: What condition is associated with SRCAP p.Ser2576del (c.7722CTC[1])?

SRCAP p.Ser2576del (c.7722CTC[1]) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.7722CTC[1] · rs797046007 · VCV212301

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

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 3.1	GERP -1.9, phastCons 1
Overall
CADD	8.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00678% European (non-Finnish) · 80/1,180,016 alleles

Filtering AF 0.00554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00527% 85/1,613,868 alleles · very rare exomes 77/1,461,854 · genomes 8/152,014 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,750
African / African-American	0.00267%	37,425
East Asian	0.00223%	44,890
South Asian	0.0022%	45,532

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.Ser2576del
Coding: c.7722CTC[1]
MANE Select: NM_006662
dbSNP: rs797046007
Type: Microsatellite
Location: chr16:30737761 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2576: 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.Ser2576Ter Pathogenic/Likely pathogenic ★★ same residue
SRCAP p.Gln2770del Uncertain significance ★★ same condition
SRCAP p.Glu3182del Uncertain significance ★★ same condition
SRCAP p.Pro2488del 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

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-ser2576del (accessed [today's date]).

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