Is CANT1 p.Ser264fs (c.789_790del) pathogenic?

CANT1 p.Ser264fs (c.789790del) is classified Pathogenic in CANT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). Very rare (popmax 8.51e-05%, nfe).

How common is CANT1 p.Ser264fs (c.789_790del) in the general population?

CANT1 p.Ser264fs (c.789_790del) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

CANT1 p.Ser264fs

c.789_790del · rs748554497 · VCV1971912

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (4 of 5, 45 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 1.4, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,272 alleles

Overall 0.000657% 1/152,178 alleles · very rare

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.Ser264fs
Coding: c.789_790del
MANE Select: NM_001159773
dbSNP: rs748554497
Type: Microsatellite
Location: chr17:78995063 (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 264: an α-helix

Full CANT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CANT1 p.Ser264= Likely benign ★ same residue
CANT1 p.Glu116fs Pathogenic ★★ same type
CANT1 p.Ser303fs Pathogenic/Likely pathogenic ★★ same type
CANT1 c.632-12_632-11del Likely benign ★ same type

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-ser264fs (accessed [today's date]).

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