Is SRCAP p.Pro2916fs (c.8726_8744dup) pathogenic?

SRCAP p.Pro2916fs (c.87268744dup) is classified Likely pathogenic in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

What condition is associated with SRCAP p.Pro2916fs (c.8726_8744dup)?

SRCAP p.Pro2916fs (c.8726_8744dup) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

SRCAP p.Pro2916fs

c.8726_8744dup · VCV4850042

Likely pathogenic Single submitter

Classification

Likely pathogenic

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	escapes	premature termination codon in the last exon (34 of 34) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 1.1, phastCons 1

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

Variant & gene context

Gene: SRCAP
Protein: p.Pro2916fs
Coding: c.8726_8744dup
MANE Select: NM_006662
Type: Duplication
Location: chr16:30738759 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2916: 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

Similar variants

SRCAP p.Pro1879fs Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Gln1247fs Likely pathogenic ★ same condition
SRCAP p.Leu2127fs Likely pathogenic ★ same condition
SRCAP p.Val826fs Likely pathogenic ★ same condition
SRCAP c.1134+3dup Uncertain significance ★ same condition
SRCAP p.Ala2409_Asn2410insGluThrGlnGlyAla Uncertain significance ★ same condition
SRCAP p.Arg1871fs Uncertain significance ★ same condition
SRCAP p.Pro2916Leu Uncertain significance ★ ⚠ same residue

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-pro2916fs (accessed [today's date]).

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