Is DMAC1 p.Thr85Met (c.254C>T) pathogenic?

DMAC1 p.Thr85Met (c.254C>T) is classified Uncertain significance in DMAC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-14). Very rare (popmax 0.00167%, amr).

How common is DMAC1 p.Thr85Met (c.254C>T) in the general population?

DMAC1 p.Thr85Met (c.254C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

DMAC1 p.Thr85Met

c.254C>T · rs766111760 · VCV3082974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.61	GERP -2
Regional constraint	o/e 1.38	unconstrained · MANE · 1,158 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	9.869	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,986 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000868% 14/1,612,748 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,184
Admixed Americangrpmax	0.00167%	59,986
European (non-Finnish)	0.000932%	107,272

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DMAC1
Protein: p.Thr85Met
Coding: c.254C>T
MANE Select: NM_033428
dbSNP: rs766111760
Type: single nucleotide variant
Location: chr9:7799481 (GRCh38)
Gene constraint: LOEUF 1.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.00

Full DMAC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAC1 p.Ala21Gly Uncertain significance ★ same type
DMAC1 p.Ala24Gly Uncertain significance ★ same type
DMAC1 p.Ala30Ser Uncertain significance ★ same type
DMAC1 p.Ala39Gly Uncertain significance ★ same type
DMAC1 p.Arg110Cys Uncertain significance ★ same type
DMAC1 p.Arg110His Uncertain significance ★ same type
DMAC1 p.Arg42His Uncertain significance ★ same type
DMAC1 p.Gln86Arg 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/dmac1-p-thr85met (accessed [today's date]).

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