Is CTNNB1 p.Ser71fs (c.211dup) pathogenic?

CTNNB1 p.Ser71fs (c.211dup) is classified Pathogenic in CTNNB1 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-09-23). Absent from gnomAD; Associated with severe intellectual disability-progressive spastic diplegia syndrome.

What condition is associated with CTNNB1 p.Ser71fs (c.211dup)?

CTNNB1 p.Ser71fs (c.211dup) is associated with severe intellectual disability-progressive spastic diplegia syndrome (ClinVar).

How common is CTNNB1 p.Ser71fs (c.211dup) in the general population?

CTNNB1 p.Ser71fs (c.211dup) is absent from gnomAD (gnomAD).

CTNNB1 p.Ser71fs

c.211dup · rs1575315766 · VCV817214

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.9	GERP -5.7

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.Ser71fs
Coding: c.211dup
MANE Select: NM_001904
dbSNP: rs1575315766
Type: Duplication
Location: chr3:41224719 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB

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.Lys233Ter Pathogenic/Likely pathogenic ★★ same condition
CTNNB1 p.Tyr333Ter Pathogenic ★★ same condition
CTNNB1 c.1185+1dup Pathogenic ★ same condition
CTNNB1 p.Ala622fs Pathogenic ★ same condition
CTNNB1 p.Cys439fs Likely pathogenic ★ same condition
CTNNB1 p.Gln85fs Pathogenic ★ same condition
CTNNB1 p.Lys158_Leu159insMetMetGlnAsnLeuProHisValGlnSerLeuAsnTerLys Pathogenic ★ same condition
CTNNB1 p.Met189fs 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-ser71fs (accessed [today's date]).

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