Is CTNNB1 p.Pro714Ser (c.2140C>T) pathogenic?

CTNNB1 p.Pro714Ser (c.2140C>T) is classified Uncertain significance in CTNNB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-17). AlphaMissense: likely benign (0.054); Very rare (popmax 0.00133%, afr); Associated with exudative vitreoretinopathy 7.

What condition is associated with CTNNB1 p.Pro714Ser (c.2140C>T)?

CTNNB1 p.Pro714Ser (c.2140C>T) is associated with exudative vitreoretinopathy 7 (ClinVar).

How common is CTNNB1 p.Pro714Ser (c.2140C>T) in the general population?

CTNNB1 p.Pro714Ser (c.2140C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Familial exudative vitreoretinopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CTNNB1 p.Pro714Ser (c.2140C>T)?

AlphaMissense predicts likely benign (score 0.054) — an in-silico prediction, not a clinical call.

CTNNB1 p.Pro714Ser

c.2140C>T · rs1260498461 · VCV2431676

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

exudative vitreoretinopathy 7

Computational evidence

Protein change
AlphaMissense	0.054	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,665 bp · p 0.012 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Overall 0.000124% 2/1,613,632 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
European (non-Finnish)	8.48e-05%	1,179,788

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTNNB1
Protein: p.Pro714Ser
Coding: c.2140C>T
MANE Select: NM_001904
dbSNP: rs1260498461
Type: single nucleotide variant
Location: chr3:41239136 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 714: the 'disordered' region; 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

exudative vitreoretinopathy 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial exudative vitreoretinopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CTNNB1 p.Pro714Arg Uncertain significance ★ ⚠ same residue
CTNNB1 p.Pro714= Likely benign ★ same residue
CTNNB1 p.Arg474Ter Pathogenic ★★ same condition
CTNNB1 p.Arg515Ter Pathogenic ★★ same condition
CTNNB1 p.Arg535Ter Pathogenic ★★ same condition
CTNNB1 p.Arg95Ter Pathogenic ★★ same condition
CTNNB1 p.Thr41Ala Likely pathogenic ★★ ⚠ same condition
CTNNB1 p.Arg710Cys 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/ctnnb1-p-pro714ser (accessed [today's date]).

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