Is ADO p.Ala146Val (c.437C>T) pathogenic?

ADO p.Ala146Val (c.437C>T) is classified Uncertain significance in ADO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1.

How common is ADO p.Ala146Val (c.437C>T) in the general population?

ADO p.Ala146Val (c.437C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADO p.Ala146Val (c.437C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

ADO p.Ala146Val

c.437C>T · rs2492275553 · VCV3089966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,537,884)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.92	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 0.78	GERP 0.84, phastCons 0.32
Regional constraint	o/e 0.92	unconstrained · MANE · 809 bp · p 0.12 · regional, not allelic
Overall
CADD	17.39	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

No allele count reported in gnomAD v4.1 (AN 1,537,884). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADO
Protein: p.Ala146Val
Coding: c.437C>T
MANE Select: NM_032804
dbSNP: rs2492275553
Type: single nucleotide variant
Location: chr10:62805496 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.28 · 9 PDB
Residue 146: the 'disordered' region; an α-helix

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

Similar variants

ADO p.Ala14Ser Uncertain significance ★ ⚠ same type
ADO p.Ala41Val 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-ala146val (accessed [today's date]).

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