Is DMTN p.Ser242Arg (c.726T>G) pathogenic?

DMTN p.Ser242Arg (c.726T>G) is classified Uncertain significance in DMTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). AlphaMissense: ambiguous (0.486); Very rare (popmax 0.0019%, amr).

How common is DMTN p.Ser242Arg (c.726T>G) in the general population?

DMTN p.Ser242Arg (c.726T>G) is very rare (popmax 0.0019%, amr) (gnomAD).

What do computational predictors say about DMTN p.Ser242Arg (c.726T>G)?

AlphaMissense predicts ambiguous (score 0.486) — an in-silico prediction, not a clinical call.

DMTN p.Ser242Arg

c.726T>G · VCV3840586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0019%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.486	ambiguous
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.89	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.27	GERP -1.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 15 kb · p 0.0007 · regional, not allelic
Overall
CADD	21.4	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 0.0019% Admixed American · 1/52,648 alleles

Overall 0.000193% 3/1,558,108 alleles · very rare exomes 3/1,406,202 · genomes 0/151,906 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0019%	52,648
Remaining individualsnot grpmax-eligible	0.00166%	60,180
South Asian	0.00117%	85,140

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.Ser242Arg
Coding: c.726T>G
MANE Select: NM_001387751
Type: single nucleotide variant
Location: chr8:22072447 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.03 · 2 PDB
Residue 242: the 'disordered' region; the 'interaction with rasgrf2' region

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-ser242arg (accessed [today's date]).

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