Is DMAC2 p.Asp205= (c.615C>T) pathogenic?

DMAC2 p.Asp205= (c.615C>T) is classified Likely benign in DMAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). Ultra-rare (popmax 0.02%, amr).

How common is DMAC2 p.Asp205= (c.615C>T) in the general population?

DMAC2 p.Asp205= (c.615C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

DMAC2 p.Asp205=

c.615C>T · rs149741041 · VCV2554116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2, phastCons 1
Overall
CADD	7.327	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,986 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00421% 68/1,613,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,999
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00449%	22,264

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.Asp205=
Coding: c.615C>T
MANE Select: NM_018035
dbSNP: rs149741041
Type: single nucleotide variant
Location: chr19:41432390 (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-asp205 (accessed [today's date]).

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