Is CDO1 p.Asn175Ser (c.524A>G) pathogenic?

CDO1 p.Asn175Ser (c.524A>G) is classified Uncertain significance in CDO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.1105); Ultra-rare (popmax 0.0165%, mid).

How common is CDO1 p.Asn175Ser (c.524A>G) in the general population?

CDO1 p.Asn175Ser (c.524A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CDO1 p.Asn175Ser (c.524A>G)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

CDO1 p.Asn175Ser

c.524A>G · rs143396814 · VCV2379066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.46	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 4.2	GERP -0.72, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	18.06	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 0.0165% Middle Eastern · 1/6,052 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00553% 89/1,609,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
East Asian	0.0156%	6,395
European (non-Finnish)	0.00636%	15,715
Remaining individualsnot grpmax-eligible	0.00481%	20,790
South Asian	0.00224%	44,733
African / African-American	0.00134%	74,806

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.Asn175Ser
Coding: c.524A>G
MANE Select: NM_001801
dbSNP: rs143396814
Type: single nucleotide variant
Location: chr5:115806398 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90 · 18 PDB
Residue 175: 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.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
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-asn175ser (accessed [today's date]).

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