Is DMD p.Arg1865Thr (c.5594G>C) pathogenic?

DMD p.Arg1865Thr (c.5594G>C) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). AlphaMissense: likely pathogenic (0.8244); Absent from gnomAD v4.1; Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg1865Thr (c.5594G>C)?

DMD p.Arg1865Thr (c.5594G>C) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg1865Thr (c.5594G>C) in the general population?

DMD p.Arg1865Thr (c.5594G>C) is absent from gnomAD v4.1 (gnomAD).

How is Duchenne 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.Arg1865Thr (c.5594G>C)?

AlphaMissense predicts likely pathogenic (score 0.8244) — an in-silico prediction, not a clinical call.

DMD p.Arg1865Thr

c.5594G>C · VCV4695579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8244 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.8244	likely pathogenic
REVEL	0.263	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.7	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

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.Arg1865Thr
Coding: c.5594G>C
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32343279 (GRCh38)
Residue 1865: the 'interaction with synm' region

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

Disease context

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

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Arg1865Gly Uncertain significance ★ same residue
DMD p.Arg1865Lys Uncertain significance ★ ⚠ same residue
DMD p.Arg1865fs Pathogenic ★★ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A 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-arg1865thr (accessed [today's date]).

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