Is CDO1 p.Ile133Leu (c.397A>C) pathogenic?

CDO1 p.Ile133Leu (c.397A>C) is classified Uncertain significance in CDO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: ambiguous (0.5392); Absent from gnomAD v4.1.

How common is CDO1 p.Ile133Leu (c.397A>C) in the general population?

CDO1 p.Ile133Leu (c.397A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDO1 p.Ile133Leu (c.397A>C)?

AlphaMissense predicts ambiguous (score 0.5392) — an in-silico prediction, not a clinical call.

CDO1 p.Ile133Leu

c.397A>C · VCV3999809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5392 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5392	ambiguous
REVEL	0.408	indeterminate
SaProt	LLR -10.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDO1
Protein: p.Ile133Leu
Coding: c.397A>C
MANE Select: NM_001801
Type: single nucleotide variant
Location: chr5:115811167 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90 · 18 PDB
Residue 133: a cross-link site; a β-strand

Full CDO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDO1 p.Ala131Val Uncertain significance ★ ⚠ same type
CDO1 p.Ala51Ser Uncertain significance ★ ⚠ same type
CDO1 p.Asn175Ser Uncertain significance ★ ⚠ same type
CDO1 p.Asn29Asp Uncertain significance ★ ⚠ same type
CDO1 p.Asn61Thr Uncertain significance ★ ⚠ same type
CDO1 p.Glu143Lys Uncertain significance ★ ⚠ same type
CDO1 p.His147Arg Uncertain significance ★ ⚠ same type
CDO1 p.His165Arg Uncertain significance ★ ⚠ 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/cdo1-p-ile133leu (accessed [today's date]).

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