Is SRCAP p.Ser1335fs (c.3996_4002dup) pathogenic?

SRCAP p.Ser1335fs (c.39964002dup) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

SRCAP p.Ser1335fs

Q: What condition is associated with SRCAP p.Ser1335fs (c.3996_4002dup)?

SRCAP p.Ser1335fs (c.3996_4002dup) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.3996_4002dup · VCV3580135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 24 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: SRCAP
Protein: p.Ser1335fs
Coding: c.3996_4002dup
MANE Select: NM_006662
Type: Duplication
Location: chr16:30723062 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1335: 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.Pro1879fs Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Ala2409fs Likely pathogenic ★ same condition
SRCAP p.Gln1247fs Likely pathogenic ★ same condition
SRCAP p.Gly2377fs Likely pathogenic ★ same condition
SRCAP p.Leu2127fs Likely pathogenic ★ same condition
SRCAP p.Pro2916fs Likely pathogenic ★ same condition
SRCAP p.Val826fs Likely pathogenic ★ same condition
SRCAP c.1134+3dup 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-ser1335fs (accessed [today's date]).

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