Is CDO1 p.His165Arg (c.494A>G) pathogenic?

CDO1 p.His165Arg (c.494A>G) is classified Uncertain significance in CDO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). AlphaMissense: likely benign (0.1286); Very rare (popmax 0.00133%, afr).

How common is CDO1 p.His165Arg (c.494A>G) in the general population?

CDO1 p.His165Arg (c.494A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CDO1 p.His165Arg (c.494A>G)?

AlphaMissense predicts likely benign (score 0.1286) — an in-silico prediction, not a clinical call.

CDO1 p.His165Arg

c.494A>G · VCV4224808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1286 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1286	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -10.14	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	21.4	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 0.00133% African / African-American · 1/75,016 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000616% 9/1,460,420 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,016
European (non-Finnish)	0.000678%	147,435

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: CDO1
Protein: p.His165Arg
Coding: c.494A>G
MANE Select: NM_001801
Type: single nucleotide variant
Location: chr5:115806428 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90 · 18 PDB
Residue 165: 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.Ile133Leu 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-his165arg (accessed [today's date]).

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