Is CANT1 p.Ala84Pro (c.250G>C) pathogenic?

CANT1 p.Ala84Pro (c.250G>C) is classified Uncertain significance in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0793); Absent from gnomAD v4.1; Associated with Desbuquois dysplasia 1.

What condition is associated with CANT1 p.Ala84Pro (c.250G>C)?

CANT1 p.Ala84Pro (c.250G>C) is associated with Desbuquois dysplasia 1 (ClinVar).

How common is CANT1 p.Ala84Pro (c.250G>C) in the general population?

CANT1 p.Ala84Pro (c.250G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CANT1 p.Ala84Pro (c.250G>C)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

CANT1 p.Ala84Pro

c.250G>C · rs767659113 · VCV325705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Desbuquois dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.75	GERP -3.3
Regional constraint	o/e 0.93	unconstrained · MANE · 594 bp · p 0.23 · regional, not allelic
Overall
CADD	6.771	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

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.Ala84Pro
Coding: c.250G>C
MANE Select: NM_001159773
dbSNP: rs767659113
Type: single nucleotide variant
Location: chr17:78997373 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.47 · 4 PDB

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

Disease context

Desbuquois dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CANT1 p.Ala84= Uncertain significance ★ same residue
CANT1 p.Ala84Thr Uncertain significance ★ ⚠ same residue
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.Trp247Arg 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-ala84pro (accessed [today's date]).

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