Is CTNNB1 p.Val613fs (c.1836_1837dup) pathogenic?

CTNNB1 p.Val613fs (c.18361837dup) is classified Pathogenic in CTNNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). Absent from gnomAD; Associated with severe intellectual disability-progressive spastic diplegia syndrome.

What condition is associated with CTNNB1 p.Val613fs (c.1836_1837dup)?

CTNNB1 p.Val613fs (c.1836_1837dup) is associated with severe intellectual disability-progressive spastic diplegia syndrome (ClinVar).

How common is CTNNB1 p.Val613fs (c.1836_1837dup) in the general population?

CTNNB1 p.Val613fs (c.1836_1837dup) is absent from gnomAD (gnomAD).

CTNNB1 p.Val613fs

c.1836_1837dup · rs2470846924 · VCV1727055

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

severe intellectual disability-progressive spastic diplegia 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	predicted	premature termination codon in exon 12 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2	GERP -4.2

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: CTNNB1
Protein: p.Val613fs
Coding: c.1836_1837dup
MANE Select: NM_001904
dbSNP: rs2470846924
Type: Microsatellite
Location: chr3:41236378 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 613: an α-helix; a UniProt-annotated variant site (in nedsdv; the patient also manifest features of exudative vitreoretinopathy)

Full CTNNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe intellectual disability-progressive spastic diplegia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTNNB1 p.Thr289fs Pathogenic ★★ same condition
CTNNB1 p.Cys619_Glu620delinsTer Likely pathogenic ★ same condition
CTNNB1 p.Tyr654fs Pathogenic ★ same condition
CTNNB1 p.Val613Gly Uncertain significance ★ ⚠ same residue
CTNNB1 p.Ser425fs Pathogenic same condition
CTNNB1 c.1082-1G>C Pathogenic ★★ same condition
CTNNB1 p.Arg474Ter Pathogenic ★★ same condition
CTNNB1 p.Arg515Ter Pathogenic ★★ 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/ctnnb1-p-val613fs (accessed [today's date]).

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