Is DMTN p.Arg366Gln (c.1097G>A) pathogenic?

DMTN p.Arg366Gln (c.1097G>A) is classified Uncertain significance in DMTN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely benign (0.1446); Very rare (popmax 0.00402%, afr).

How common is DMTN p.Arg366Gln (c.1097G>A) in the general population?

DMTN p.Arg366Gln (c.1097G>A) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about DMTN p.Arg366Gln (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.1446) — an in-silico prediction, not a clinical call.

DMTN p.Arg366Gln

c.1097G>A · rs755561897 · VCV2455000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1446	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 15 kb · p 0.0007 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.00402% African / African-American · 3/74,616 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.00118% 19/1,613,206 alleles · very rare exomes 16/1,461,772 · genomes 3/151,434 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,872
East Asian	0.00223%	44,820
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.0011%	90,761
South Asian	0.0011%	91,050

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: DMTN
Protein: p.Arg366Gln
Coding: c.1097G>A
MANE Select: NM_001387751
dbSNP: rs755561897
Type: single nucleotide variant
Location: chr8:22081186 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.03 · 2 PDB
Residue 366: the hp domain; an α-helix

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

Similar variants

DMTN c.295-2A>T Uncertain significance ★ same type
DMTN c.604+2T>G Uncertain significance ★ same type
DMTN p.Ala199Gly Uncertain significance ★ ⚠ same type
DMTN p.Arg135Cys Uncertain significance ★ ⚠ same type
DMTN p.Arg150Lys Uncertain significance ★ ⚠ same type
DMTN p.Arg208Trp Uncertain significance ★ ⚠ same type
DMTN p.Arg212Trp Uncertain significance ★ ⚠ same type
DMTN p.Arg236Leu 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/dmtn-p-arg366gln (accessed [today's date]).

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