Is SRCAP p.Ala454fs (c.1358dup) pathogenic?

SRCAP p.Ala454fs (c.1358dup) is classified Pathogenic in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Ala454fs (c.1358dup)?

SRCAP p.Ala454fs (c.1358dup) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Ala454fs (c.1358dup) in the general population?

SRCAP p.Ala454fs (c.1358dup) is no gnomAD frequency available for this variant (gnomAD).

SRCAP p.Ala454fs

c.1358dup · rs2506628039 · VCV3169835

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 11 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.58	GERP -1.8, phastCons 0.87

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SRCAP
Protein: p.Ala454fs
Coding: c.1358dup
MANE Select: NM_006662
dbSNP: rs2506628039
Type: Duplication
Location: chr16:30711608 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 454: a UniProt-annotated variant site (in dehmba); the 'disordered' region

Full SRCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Gly569fs Pathogenic ★ same condition
SRCAP p.Ala454Ser Uncertain significance ★ same residue
SRCAP p.Ala454Val Uncertain significance ★ same residue
SRCAP p.Ala454= Likely benign ★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr 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-ala454fs (accessed [today's date]).

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