Is DMAC2 p.Arg168Cys (c.502C>T) pathogenic?

DMAC2 p.Arg168Cys (c.502C>T) is classified Uncertain significance in DMAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.194); Ultra-rare (popmax 0.0878%, sas).

How common is DMAC2 p.Arg168Cys (c.502C>T) in the general population?

DMAC2 p.Arg168Cys (c.502C>T) is ultra-rare (popmax 0.0878%, sas) (gnomAD).

What do computational predictors say about DMAC2 p.Arg168Cys (c.502C>T)?

AlphaMissense predicts likely benign (score 0.194) — an in-silico prediction, not a clinical call.

DMAC2 p.Arg168Cys

c.502C>T · rs782413672 · VCV3082986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.194 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0878%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.194	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -10.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,665 bp · p 0.25 · regional, not allelic
Overall
CADD	28.9	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 0.0878% South Asian · 80/91,068 alleles

Filtering AF 0.0723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0666%

Overall 0.00577% 93/1,612,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0878%	1,138
Remaining individualsnot grpmax-eligible	0.0112%	8,925
East Asian	0.00223%	44,880
Admixed American	0.00167%	60,014
European (non-Finnish)	0.000339%	294,951

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.Arg168Cys
Coding: c.502C>T
MANE Select: NM_018035
dbSNP: rs782413672
Type: single nucleotide variant
Location: chr19:41433366 (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-arg168cys (accessed [today's date]).

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