Is SRCAP p.Pro2488del (c.7452TCC[1]) pathogenic?

SRCAP p.Pro2488del (c.7452TCC[1]) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-12). Very rare (popmax 0.00677%, amr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Pro2488del (c.7452TCC[1]) in the general population?

SRCAP p.Pro2488del (c.7452TCC[1]) is very rare (popmax 0.00677%, amr) (gnomAD).

SRCAP p.Pro2488del

Q: What condition is associated with SRCAP p.Pro2488del (c.7452TCC[1])?

SRCAP p.Pro2488del (c.7452TCC[1]) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.7452TCC[1] · VCV3580213

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00677%, amr)

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 1	GERP -4.2, phastCons 1
Region caveats
Repeat context	tandem	(CCT)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00677% Admixed American · 4/59,106 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000251% 4/1,596,254 alleles · very rare exomes 4/1,444,210 · genomes 0/152,044 · joint denominator

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.Pro2488del
Coding: c.7452TCC[1]
MANE Select: NM_006662
Type: Microsatellite
Location: chr16:30737491 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2488: 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.Glu3182del 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-pro2488del (accessed [today's date]).

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