Is CANT1 p.Phe49= (c.147C>T) pathogenic?

CANT1 p.Phe49= (c.147C>T) is classified Conflicting classifications of pathogenicity in CANT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-10). Ultra-rare (popmax 0.0444%, nfe); Associated with Desbuquois dysplasia 1.

What condition is associated with CANT1 p.Phe49= (c.147C>T)?

CANT1 p.Phe49= (c.147C>T) is associated with Desbuquois dysplasia 1 (ClinVar).

How common is CANT1 p.Phe49= (c.147C>T) in the general population?

CANT1 p.Phe49= (c.147C>T) is ultra-rare (popmax 0.0444%, nfe) (gnomAD).

CANT1 p.Phe49=

c.147C>T · rs371500993 · VCV747885

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0444%, nfe)

Conditions

Desbuquois dysplasia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -2, phastCons 0.84
Overall
CADD	4.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0444% European (non-Finnish) · 518/1,166,896 alleles

Filtering AF 0.0412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.0342% 545/1,591,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0444%	2,253
Admixed American	0.0204%	4,912
Remaining individualsnot grpmax-eligible	0.0179%	5,583
African / African-American	0.00403%	24,841
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,290

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.Phe49=
Coding: c.147C>T
MANE Select: NM_001159773
dbSNP: rs371500993
Type: single nucleotide variant
Location: chr17:78997476 (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 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
CANT1 c.835+6A>G 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-phe49 (accessed [today's date]).

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