Is CANT1 p.Arg19Gln (c.56G>A) pathogenic?

CANT1 p.Arg19Gln (c.56G>A) is classified Conflicting classifications of pathogenicity in CANT1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1236); Rare (popmax 0.28%, nfe); Associated with Desbuquois dysplasia 1.

What condition is associated with CANT1 p.Arg19Gln (c.56G>A)?

CANT1 p.Arg19Gln (c.56G>A) is associated with Desbuquois dysplasia 1 (ClinVar).

How common is CANT1 p.Arg19Gln (c.56G>A) in the general population?

CANT1 p.Arg19Gln (c.56G>A) is rare (popmax 0.28%, nfe) (gnomAD).

What do computational predictors say about CANT1 p.Arg19Gln (c.56G>A)?

AlphaMissense predicts likely benign (score 0.1236) — an in-silico prediction, not a clinical call.

CANT1 p.Arg19Gln

c.56G>A · rs144060377 · VCV279729

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1236 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Desbuquois dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.1236	likely benign
REVEL	0.559	indeterminate
SaProt	LLR -6.98	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	29.4	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 0.28% European (non-Finnish) · 3,234/1,154,442 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.22% 3,440/1,562,990 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.28%	357
Remaining individualsnot grpmax-eligible	0.173%	578
Admixed American	0.0563%	1,777
African / African-American	0.053%	1,885
Middle Eastern	0.0344%	2,911
Finnishnot grpmax-eligible	0.0293%	3,414
East Asian	0.0136%	7,363
South Asian	0.00724%	13,812
Ashkenazi Jewishnot grpmax-eligible	0.0038%	26,344

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.Arg19Gln
Coding: c.56G>A
MANE Select: NM_001159773
dbSNP: rs144060377
Type: single nucleotide variant
Location: chr17:78997567 (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.Arg19Trp 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-arg19gln (accessed [today's date]).

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