Is CANT1 p.Pro245Leu (c.734C>T) pathogenic?

CANT1 p.Pro245Leu (c.734C>T) is classified Pathogenic/Likely pathogenic in CANT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.7512); Ultra-rare (popmax 0.0164%, mid); Associated with Desbuquois dysplasia 1.

What condition is associated with CANT1 p.Pro245Leu (c.734C>T)?

CANT1 p.Pro245Leu (c.734C>T) is associated with Desbuquois dysplasia 1, epiphyseal dysplasia, multiple, 7 (ClinVar).

How common is CANT1 p.Pro245Leu (c.734C>T) in the general population?

CANT1 p.Pro245Leu (c.734C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CANT1 p.Pro245Leu (c.734C>T)?

AlphaMissense predicts likely pathogenic (score 0.7512) — an in-silico prediction, not a clinical call.

CANT1 p.Pro245Leu

c.734C>T · rs761853610 · VCV452497

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7512 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Desbuquois dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.7512	likely pathogenic ✓ concordant with ClinVar
REVEL	0.731	pathogenic-leaning
SaProt	LLR -12.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 1,942 bp · p 0.00015 · regional, not allelic
Overall
CADD	29.2	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00155% 25/1,613,554 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Finnishnot grpmax-eligible	0.00469%	21,319
Remaining individualsnot grpmax-eligible	0.0032%	31,234
South Asian	0.0022%	45,453
European (non-Finnish)	0.00136%	73,743
African / African-American	0.00133%	74,920

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.Pro245Leu
Coding: c.734C>T
MANE Select: NM_001159773
dbSNP: rs761853610
Type: single nucleotide variant
Location: chr17:78995119 (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 245: an α-helix

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

Also linked: epiphyseal dysplasia, multiple, 7

Similar variants

CANT1 p.Pro245= Conflicting classifications of pathogenicity ★ same residue
CANT1 p.Pro245fs Pathogenic 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.Pro299Leu Likely pathogenic ★★ same condition
CANT1 p.Trp247Arg Likely pathogenic ★★ same condition
CANT1 p.Val226Met 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-pro245leu (accessed [today's date]).

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