Is ADAR p.Ala672Val (c.2015C>T) pathogenic?

ADAR p.Ala672Val (c.2015C>T) is classified Uncertain significance in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.8923); Absent from gnomAD v4.1.

How common is ADAR p.Ala672Val (c.2015C>T) in the general population?

ADAR p.Ala672Val (c.2015C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAR p.Ala672Val (c.2015C>T)?

AlphaMissense predicts likely pathogenic (score 0.8923) — an in-silico prediction, not a clinical call.

ADAR p.Ala672Val

c.2015C>T · VCV3765752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8923	likely pathogenic
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -11.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 17 kb · p 1.3e-17 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ADAR
Protein: p.Ala672Val
Coding: c.2015C>T
MANE Select: NM_001111
Type: single nucleotide variant
Location: chr1:154597187 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 672: the drbm 2 domain

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

Similar variants

ADAR p.Ala672= Likely benign ★ same residue
ADAR c.2885+1G>A Likely pathogenic ★★ same type
ADAR p.Arg1078Cys Pathogenic ★★ same type
ADAR p.Arg1096Ter Pathogenic/Likely pathogenic ★★ same type
ADAR p.Arg328Ter Pathogenic ★★ same type
ADAR p.Arg360Ter Pathogenic/Likely pathogenic ★★ same type
ADAR p.Arg474Ter Pathogenic ★★ same type
ADAR p.Arg534Ter Pathogenic ★★ 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/adar-p-ala672val (accessed [today's date]).

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