Is CANT1 p.Trp247Arg (c.739T>C) pathogenic?

CANT1 p.Trp247Arg (c.739T>C) is classified Likely pathogenic in CANT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-27). AlphaMissense: likely pathogenic (0.9865); Very rare (popmax 0.000593%, nfe); Associated with Joint dislocation.

What condition is associated with CANT1 p.Trp247Arg (c.739T>C)?

CANT1 p.Trp247Arg (c.739T>C) is associated with Joint dislocation, Desbuquois dysplasia 1, epiphyseal dysplasia, multiple, 7 (ClinVar).

How common is CANT1 p.Trp247Arg (c.739T>C) in the general population?

CANT1 p.Trp247Arg (c.739T>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CANT1 p.Trp247Arg (c.739T>C)?

AlphaMissense predicts likely pathogenic (score 0.9865) — an in-silico prediction, not a clinical call.

CANT1 p.Trp247Arg

c.739T>C · rs1361897950 · VCV929439

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joint dislocation

Computational evidence

Protein change
AlphaMissense	0.9865	likely pathogenic ✓ concordant with ClinVar · top 4% in CANT1
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -14.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 1,942 bp · p 0.00015 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,682 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,154 alleles · very rare

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: CANT1
Protein: p.Trp247Arg
Coding: c.739T>C
MANE Select: NM_001159773
dbSNP: rs1361897950
Type: single nucleotide variant
Location: chr17:78995114 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.47 · 4 PDB
Residue 247: a β-strand

Full CANT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joint dislocation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Desbuquois dysplasia 1 epiphyseal dysplasia, multiple, 7

Similar variants

CANT1 c.836-9G>A Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Arg300Cys Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Glu215Lys Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Pro245Leu Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Pro299Leu Likely pathogenic ★★ same condition
CANT1 p.Val226Met Pathogenic ★★ same condition
CANT1 c.835+6A>G Uncertain significance ★★ same condition
CANT1 c.-23+94T>G 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/cant1-p-trp247arg (accessed [today's date]).

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