Is DMD p.Glu1874Lys (c.5620G>A) pathogenic?

DMD p.Glu1874Lys (c.5620G>A) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). AlphaMissense: ambiguous (0.4201); Rare (popmax 0.364%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Glu1874Lys (c.5620G>A)?

DMD p.Glu1874Lys (c.5620G>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Glu1874Lys (c.5620G>A) in the general population?

DMD p.Glu1874Lys (c.5620G>A) is rare (popmax 0.364%, afr) (gnomAD).

What do computational predictors say about DMD p.Glu1874Lys (c.5620G>A)?

AlphaMissense predicts ambiguous (score 0.4201) — an in-silico prediction, not a clinical call.

DMD p.Glu1874Lys

c.5620G>A · rs142441725 · VCV94675

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

ambiguous

0.4201 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.364%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4201	ambiguous
REVEL	0.185	benign-leaning
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	23.3	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 0.364% African / African-American · 207/56,874 alleles

Filtering AF 0.323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.308%

Overall 0.0204% 246/1,206,757 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.364%	275
Remaining individualsnot grpmax-eligible	0.0421%	2,376
Admixed American	0.0285%	3,505
South Asian	0.00176%	56,681
European (non-Finnish)	0.00056%	178,601

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: DMD
Protein: p.Glu1874Lys
Coding: c.5620G>A
MANE Select: NM_004006
dbSNP: rs142441725
Type: single nucleotide variant
Location: chrX:32343253 (GRCh38)
Residue 1874: the 'interaction with synm' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

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
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G Likely pathogenic ★★ same condition
DMD c.10554-2A>G Pathogenic/Likely 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-glu1874lys (accessed [today's date]).

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