Is DMAC2 p.Gly95Glu (c.284G>A) pathogenic?

DMAC2 p.Gly95Glu (c.284G>A) is classified Uncertain significance in DMAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: ambiguous (0.4492); Very rare (popmax 0.0022%, sas).

How common is DMAC2 p.Gly95Glu (c.284G>A) in the general population?

DMAC2 p.Gly95Glu (c.284G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DMAC2 p.Gly95Glu (c.284G>A)?

AlphaMissense predicts ambiguous (score 0.4492) — an in-silico prediction, not a clinical call.

DMAC2 p.Gly95Glu

c.284G>A · rs1555771174 · VCV2618237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4492	ambiguous
REVEL	0.662	pathogenic-leaning
SaProt	LLR -11.14	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,665 bp · p 0.25 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000137% 2/1,461,844 alleles · very rare

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: DMAC2
Protein: p.Gly95Glu
Coding: c.284G>A
MANE Select: NM_018035
dbSNP: rs1555771174
Type: single nucleotide variant
Location: chr19:41436404 (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.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
DMAC2 p.Arg146His 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-gly95glu (accessed [today's date]).

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