Is SRCAP p.Gly2377fs (c.7127dup) pathogenic?

SRCAP p.Gly2377fs (c.7127dup) is classified Likely pathogenic in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Gly2377fs (c.7127dup)?

SRCAP p.Gly2377fs (c.7127dup) is associated with Floating-Harbor syndrome (ClinVar).

SRCAP p.Gly2377fs

c.7127dup · VCV4292679

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Floating-Harbor syndrome

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 2.4	GERP 2.3, phastCons 1

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

Variant & gene context

Gene: SRCAP
Protein: p.Gly2377fs
Coding: c.7127dup
MANE Select: NM_006662
Type: Duplication
Location: chr16:30737165 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2377: 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

Floating-Harbor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Pro1879fs Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Ala2409fs Likely pathogenic ★ same condition
SRCAP c.1134+3dup Uncertain significance ★ same condition
SRCAP c.6729+9dup Uncertain significance ★ same condition
SRCAP p.Ala2409_Asn2410insGluThrGlnGlyAla Uncertain significance ★ same condition
SRCAP p.Arg1871fs Uncertain significance ★ same condition
SRCAP p.Met1415fs Uncertain significance ★ same condition
SRCAP p.Ser1335fs 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-gly2377fs (accessed [today's date]).

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