Is ADO p.Asp215Val (c.644A>T) pathogenic?

ADO p.Asp215Val (c.644A>T) is classified Uncertain significance in ADO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.3746); Absent from gnomAD v4.1.

How common is ADO p.Asp215Val (c.644A>T) in the general population?

ADO p.Asp215Val (c.644A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADO p.Asp215Val (c.644A>T)?

AlphaMissense predicts ambiguous (score 0.3746) — an in-silico prediction, not a clinical call.

ADO p.Asp215Val

c.644A>T · VCV4244893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3746 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3746	ambiguous
REVEL	0.169	moderately benign-leaning
SaProt	LLR -11.25	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.83, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 809 bp · p 0.12 · regional, not allelic
Overall
CADD	24.1	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: ADO
Protein: p.Asp215Val
Coding: c.644A>T
MANE Select: NM_032804
Type: single nucleotide variant
Location: chr10:62805703 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.28 · 9 PDB
Residue 215: an α-helix

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.Ala41Val Uncertain significance ★ ⚠ same type
ADO p.Arg230Gly Uncertain significance ★ ⚠ same type
ADO p.Arg33Cys 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-asp215val (accessed [today's date]).

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