Is CANT1 p.Pro69Ser (c.205C>T) pathogenic?

CANT1 p.Pro69Ser (c.205C>T) is classified Uncertain significance in CANT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0649); Ultra-rare (popmax 0.0335%, eas); Associated with Inborn genetic diseases.

What condition is associated with CANT1 p.Pro69Ser (c.205C>T)?

CANT1 p.Pro69Ser (c.205C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CANT1 p.Pro69Ser (c.205C>T) in the general population?

CANT1 p.Pro69Ser (c.205C>T) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

What do computational predictors say about CANT1 p.Pro69Ser (c.205C>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

CANT1 p.Pro69Ser

c.205C>T · rs577520073 · VCV2159917

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -3.3, phastCons 0.048
Regional constraint	o/e 0.93	unconstrained · MANE · 594 bp · p 0.23 · regional, not allelic
Overall
CADD	0.078	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 0.0335% East Asian · 15/44,724 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00206% 33/1,605,394 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0335%	2,982
Remaining individualsnot grpmax-eligible	0.0129%	7,765
South Asian	0.0055%	18,190
African / African-American	0.00401%	24,930
European (non-Finnish)	0.00017%	586,982

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.Pro69Ser
Coding: c.205C>T
MANE Select: NM_001159773
dbSNP: rs577520073
Type: single nucleotide variant
Location: chr17:78997418 (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

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.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
CANT1 p.Asn88Asp 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-pro69ser (accessed [today's date]).

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