Is CANT1 p.Ala371Pro (c.1111G>C) pathogenic?

CANT1 p.Ala371Pro (c.1111G>C) is classified Likely pathogenic in CANT1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.938); Absent from gnomAD v4.1; Associated with epiphyseal dysplasia, multiple, 7.

What condition is associated with CANT1 p.Ala371Pro (c.1111G>C)?

CANT1 p.Ala371Pro (c.1111G>C) is associated with epiphyseal dysplasia, multiple, 7 (ClinVar).

How common is CANT1 p.Ala371Pro (c.1111G>C) in the general population?

CANT1 p.Ala371Pro (c.1111G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CANT1 p.Ala371Pro (c.1111G>C)?

AlphaMissense predicts likely pathogenic (score 0.938) — an in-silico prediction, not a clinical call.

CANT1 p.Ala371Pro

c.1111G>C · VCV4819343

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.938 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epiphyseal dysplasia, multiple, 7

Computational evidence

Protein change
AlphaMissense	0.938	likely pathogenic ✓ concordant with ClinVar
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -10.69	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,531 bp · p 0.53 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CANT1
Protein: p.Ala371Pro
Coding: c.1111G>C
MANE Select: NM_001159773
Type: single nucleotide variant
Location: chr17:78993645 (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 371: a β-strand

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

Disease context

epiphyseal dysplasia, multiple, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple epiphyseal dysplasia type 7 (Orphanet):

Onset: Childhood

Similar variants

CANT1 p.Ala371Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CANT1 p.Ala371= Likely benign ★★ same residue
CANT1 c.836-9G>A Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Pro245Leu Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Trp247Arg Likely pathogenic ★★ same condition
CANT1 p.Val226Met Pathogenic ★★ same condition
CANT1 p.Val208Met Uncertain significance ★★ ⚠ same condition
CANT1 p.Ile171Phe Likely 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/cant1-p-ala371pro (accessed [today's date]).

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