Is CANT1 p.Arg40His (c.119G>A) pathogenic?

CANT1 p.Arg40His (c.119G>A) is classified Uncertain significance in CANT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-25). AlphaMissense: likely benign (0.0954); Very rare (popmax 0.00674%, afr); Associated with Desbuquois dysplasia 1.

What condition is associated with CANT1 p.Arg40His (c.119G>A)?

CANT1 p.Arg40His (c.119G>A) is associated with Desbuquois dysplasia 1 (ClinVar).

How common is CANT1 p.Arg40His (c.119G>A) in the general population?

CANT1 p.Arg40His (c.119G>A) is very rare (popmax 0.00674%, afr) (gnomAD).

What do computational predictors say about CANT1 p.Arg40His (c.119G>A)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CANT1 p.Arg40His

c.119G>A · rs375819727 · VCV890249

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00674%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Desbuquois dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.56	indeterminate
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 594 bp · p 0.23 · regional, not allelic
Overall
CADD	23.4	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 0.00674% African / African-American · 5/74,152 alleles

Filtering AF 0.00296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.00337% 53/1,574,946 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00674%	14,830
European (non-Finnish)	0.00388%	25,755
Remaining individualsnot grpmax-eligible	0.0033%	30,343
East Asian	0.00225%	44,350

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.Arg40His
Coding: c.119G>A
MANE Select: NM_001159773
dbSNP: rs375819727
Type: single nucleotide variant
Location: chr17:78997504 (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

Desbuquois dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CANT1 p.Arg40Cys Uncertain significance ★ ⚠ 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.Pro245Leu 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-arg40his (accessed [today's date]).

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