Is CANT1 p.Leu93Pro (c.278T>C) pathogenic?

CANT1 p.Leu93Pro (c.278T>C) is classified Uncertain significance in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely pathogenic (0.6784); Very rare (popmax 0.0055%, sas); Associated with Inborn genetic diseases.

What condition is associated with CANT1 p.Leu93Pro (c.278T>C)?

CANT1 p.Leu93Pro (c.278T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CANT1 p.Leu93Pro (c.278T>C) in the general population?

CANT1 p.Leu93Pro (c.278T>C) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CANT1 p.Leu93Pro (c.278T>C)?

AlphaMissense predicts likely pathogenic (score 0.6784) — an in-silico prediction, not a clinical call.

CANT1 p.Leu93Pro

c.278T>C · VCV3263124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6784	likely pathogenic
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -14.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.23	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 594 bp · p 0.23 · regional, not allelic
Overall
CADD	25.0	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 0.0055% South Asian · 5/90,838 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000549% 8/1,456,560 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,168
Finnishnot grpmax-eligible	0.00317%	31,541
European (non-Finnish)	8.5e-05%	1,175,818

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.Leu93Pro
Coding: c.278T>C
MANE Select: NM_001159773
Type: single nucleotide variant
Location: chr17:78997345 (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 93: a β-strand

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.Leu93fs Pathogenic ★★ same residue
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

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-leu93pro (accessed [today's date]).

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