Is DMD p.Met230Arg (c.689T>G) pathogenic?

DMD p.Met230Arg (c.689T>G) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). AlphaMissense: likely pathogenic (0.9622); Absent from gnomAD v4.1; Associated with Becker muscular dystrophy.

What condition is associated with DMD p.Met230Arg (c.689T>G)?

DMD p.Met230Arg (c.689T>G) is associated with Becker muscular dystrophy (ClinVar).

How common is DMD p.Met230Arg (c.689T>G) in the general population?

DMD p.Met230Arg (c.689T>G) is absent from gnomAD v4.1 (gnomAD).

How is Becker muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Met230Arg (c.689T>G)?

AlphaMissense predicts likely pathogenic (score 0.9622) — an in-silico prediction, not a clinical call.

DMD p.Met230Arg

c.689T>G · rs2147606547 · VCV1806438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9622 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Becker muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9622	likely pathogenic · top 7% in DMD
REVEL	0.902	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.3	GERP 6, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Met230Arg
Coding: c.689T>G
MANE Select: NM_004006
dbSNP: rs2147606547
Type: single nucleotide variant
Location: chrX:32699254 (GRCh38)
Residue 230: an α-helix; the calponin-homology (ch) 2 domain; the 'actin-binding' region

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

Disease context

Becker muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Becker muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DMD p.Met230Ile Uncertain significance ★ ⚠ same residue
DMD p.Met230Lys Uncertain significance ★ ⚠ same residue
DMD p.Met230Thr Uncertain significance ★ ⚠ same residue
DMD c.10921+2T>C Likely pathogenic ★★ same condition
DMD c.1704+1G>T Pathogenic ★★ same condition
DMD c.1705-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.1812+1G>A Pathogenic/Likely pathogenic ★★ same condition
DMD c.2623-2A>G Pathogenic ★★ same condition

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/dmd-p-met230arg (accessed [today's date]).

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