Is SRCAP p.Thr1147del (c.3432CAC[2]) pathogenic?

SRCAP p.Thr1147del (c.3432CAC[2]) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). Ultra-rare (popmax 0.0472%, sas); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Thr1147del (c.3432CAC[2]) in the general population?

SRCAP p.Thr1147del (c.3432CAC[2]) is ultra-rare (popmax 0.0472%, sas) (gnomAD).

SRCAP p.Thr1147del

Q: What condition is associated with SRCAP p.Thr1147del (c.3432CAC[2])?

SRCAP p.Thr1147del (c.3432CAC[2]) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.3432CAC[2] · VCV3580114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0472%, sas)

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 6.4	GERP 0.21, phastCons 1
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CCA)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0472% South Asian · 43/91,088 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00279% 45/1,614,044 alleles · ultra-rare exomes 43/1,461,714 · genomes 2/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0472%	2,118
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,048

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.Thr1147del
Coding: c.3432CAC[2]
MANE Select: NM_006662
Type: Microsatellite
Location: chr16:30721366 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1147: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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.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

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-thr1147del (accessed [today's date]).

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