Is DMAC2 p.Val231Ala (c.692T>C) pathogenic?

DMAC2 p.Val231Ala (c.692T>C) is classified Uncertain significance in DMAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: ambiguous (0.5492); Absent from gnomAD v4.1.

How common is DMAC2 p.Val231Ala (c.692T>C) in the general population?

DMAC2 p.Val231Ala (c.692T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMAC2 p.Val231Ala (c.692T>C)?

AlphaMissense predicts ambiguous (score 0.5492) — an in-silico prediction, not a clinical call.

DMAC2 p.Val231Ala

c.692T>C · rs2513472578 · VCV3082993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5492 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5492	ambiguous
REVEL	0.276	benign-leaning
SaProt	LLR -13.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,665 bp · p 0.25 · regional, not allelic
Overall
CADD	23.3	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: DMAC2
Protein: p.Val231Ala
Coding: c.692T>C
MANE Select: NM_018035
dbSNP: rs2513472578
Type: single nucleotide variant
Location: chr19:41432313 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.56

Full DMAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAC2 p.Val231= Likely benign ★ same residue
DMAC2 p.His23Arg Likely benign ★★ same type
DMAC2 p.Ala193Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Ala237Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Ala27Val Uncertain significance ★ ⚠ same type
DMAC2 p.Ala86Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Arg107Ser Uncertain significance ★ ⚠ same type
DMAC2 p.Arg146Gly 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/dmac2-p-val231ala (accessed [today's date]).

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