Is ADO p.Ala41Val (c.122C>T) pathogenic?

ADO p.Ala41Val (c.122C>T) is classified Uncertain significance in ADO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.0778); Ultra-rare (popmax 0.0113%, eas).

How common is ADO p.Ala41Val (c.122C>T) in the general population?

ADO p.Ala41Val (c.122C>T) is ultra-rare (popmax 0.0113%, eas) (gnomAD).

What do computational predictors say about ADO p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

ADO p.Ala41Val

c.122C>T · rs776538639 · VCV2365430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.21	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 0.65	GERP 0.92, phastCons 0.054
Regional constraint	o/e 0.92	unconstrained · MANE · 809 bp · p 0.12 · regional, not allelic
Overall
CADD	17.08	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 0.0113% East Asian · 5/44,438 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00278%

Overall 0.00156% 25/1,600,096 alleles · ultra-rare exomes 23/1,447,938 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0113%	8,888
Admixed American	0.00509%	19,654
Remaining individualsnot grpmax-eligible	0.00161%	61,956
European (non-Finnish)	0.00136%	73,542

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: ADO
Protein: p.Ala41Val
Coding: c.122C>T
MANE Select: NM_032804
dbSNP: rs776538639
Type: single nucleotide variant
Location: chr10:62805181 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.28 · 9 PDB
Residue 41: the 'disordered' region

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

Similar variants

ADO p.Ala146Val Uncertain significance ★ ⚠ same type
ADO p.Ala14Ser Uncertain significance ★ ⚠ same type
ADO p.Arg230Gly Uncertain significance ★ ⚠ same type
ADO p.Arg33Cys Uncertain significance ★ ⚠ same type
ADO p.Asp215Val Uncertain significance ★ ⚠ same type
ADO p.Asp219Glu Uncertain significance ★ ⚠ same type
ADO p.Asp34His Uncertain significance ★ ⚠ same type
ADO p.Asp94Glu 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/ado-p-ala41val (accessed [today's date]).

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