Is CANT1 p.Trp288Arg (c.862T>C) pathogenic?

CANT1 p.Trp288Arg (c.862T>C) is classified Uncertain significance in CANT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-01-02). AlphaMissense: likely pathogenic (0.9849); Very rare (popmax 0.00227%, eas).

How common is CANT1 p.Trp288Arg (c.862T>C) in the general population?

CANT1 p.Trp288Arg (c.862T>C) is very rare (popmax 0.00227%, eas) (gnomAD).

What do computational predictors say about CANT1 p.Trp288Arg (c.862T>C)?

AlphaMissense predicts likely pathogenic (score 0.9849) — an in-silico prediction, not a clinical call.

CANT1 p.Trp288Arg

c.862T>C · rs794727655 · VCV197370

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9849	likely pathogenic · top 4% in CANT1
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -13.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,531 bp · p 0.53 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00227% East Asian · 1/44,088 alleles

Overall 6.95e-05% 1/1,438,702 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.Trp288Arg
Coding: c.862T>C
MANE Select: NM_001159773
dbSNP: rs794727655
Type: single nucleotide variant
Location: chr17:78993894 (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 288: a β-strand

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

Similar variants

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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
CANT1 p.Trp86Ter Pathogenic/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-trp288arg (accessed [today's date]).

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