Is CANT1 p.Pro95Ala (c.283C>G) pathogenic?

CANT1 p.Pro95Ala (c.283C>G) is classified Likely benign in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely benign (0.0538); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CANT1 p.Pro95Ala (c.283C>G)?

CANT1 p.Pro95Ala (c.283C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CANT1 p.Pro95Ala (c.283C>G) in the general population?

CANT1 p.Pro95Ala (c.283C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CANT1 p.Pro95Ala (c.283C>G)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

CANT1 p.Pro95Ala

c.283C>G · rs1206876278 · VCV3136976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.35	acceptor loss, 11 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.19	GERP -3.2
Regional constraint	o/e 0.93	unconstrained · MANE · 594 bp · p 0.23 · regional, not allelic
Overall
CADD	4.029	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 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,457
European (non-Finnish)	0.000508%	196,675

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.Pro95Ala
Coding: c.283C>G
MANE Select: NM_001159773
dbSNP: rs1206876278
Type: single nucleotide variant
Location: chr17:78997340 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CANT1 p.Arg300Cys Pathogenic/Likely pathogenic ★★ same condition
CANT1 p.Arg183Gln Uncertain significance ★★ ⚠ same condition
CANT1 p.Arg183Trp Uncertain significance ★★ ⚠ same condition
CANT1 p.Arg270Gln Uncertain significance ★★ ⚠ same condition
CANT1 p.Arg38His Uncertain significance ★★ ⚠ same condition
CANT1 p.Arg63His Uncertain significance ★★ ⚠ same condition
CANT1 p.Arg63Ser Uncertain significance ★★ ⚠ same condition
CANT1 p.Asn88Asp 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-pro95ala (accessed [today's date]).

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