Is CANT1 p.Ala331Thr (c.991G>A) pathogenic?

CANT1 p.Ala331Thr (c.991G>A) is classified Uncertain significance in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-03). AlphaMissense: likely benign (0.0594); Ultra-rare (popmax 0.0165%, mid).

How common is CANT1 p.Ala331Thr (c.991G>A) in the general population?

CANT1 p.Ala331Thr (c.991G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CANT1 p.Ala331Thr (c.991G>A)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

CANT1 p.Ala331Thr

c.991G>A · rs1345658200 · VCV1943868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.24	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 -3	GERP -3.2
Regional constraint	o/e 1.04	unconstrained · MANE · 1,531 bp · p 0.53 · regional, not allelic
Overall
CADD	0.013	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 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000342% 5/1,460,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0048%	20,832
European (non-Finnish)	8.47e-05%	1,179,997

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.Ala331Thr
Coding: c.991G>A
MANE Select: NM_001159773
dbSNP: rs1345658200
Type: single nucleotide variant
Location: chr17:78993765 (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 331: a β-strand

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

Similar variants

CANT1 p.Ala331Val Uncertain significance ★ ⚠ same residue
CANT1 c.836-9G>A Pathogenic/Likely pathogenic ★★ same type
CANT1 p.Arg300Cys Pathogenic/Likely pathogenic ★★ same type
CANT1 p.Glu215Lys Pathogenic/Likely pathogenic ★★ same type
CANT1 p.Glu215Ter Pathogenic ★★ same type
CANT1 p.Pro245Leu Pathogenic/Likely pathogenic ★★ same type
CANT1 p.Pro299Leu Likely pathogenic ★★ same type
CANT1 p.Trp247Arg Likely pathogenic ★★ same type

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-ala331thr (accessed [today's date]).

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