Is DMD p.Arg48= (c.144G>A) pathogenic?

DMD p.Arg48= (c.144G>A) is classified Likely benign in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-11). Very rare (popmax 0.00174%, afr); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg48= (c.144G>A)?

DMD p.Arg48= (c.144G>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg48= (c.144G>A) in the general population?

DMD p.Arg48= (c.144G>A) is very rare (popmax 0.00174%, afr) (gnomAD).

How is Duchenne muscular dystrophy inherited?

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

DMD p.Arg48=

c.144G>A · rs577671071 · VCV385831

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -2.5, phastCons 1
Overall
CADD	8.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,601 alleles

Overall 0.00073% 8/1,096,630 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0126%	7,927
African / African-Americangrpmax	0.00174%	57,601
European (non-Finnish)	0.000112%	894,118

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg48=
Coding: c.144G>A
MANE Select: NM_004006
dbSNP: rs577671071
Type: single nucleotide variant
Location: chrX:32849770 (GRCh38)
Residue 48: the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region; a UniProt-annotated variant site (in bmd)

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.Arg48Lys Likely benign ★ same residue
DMD p.Arg48fs 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
DMD c.10223+1G>C 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-arg48 (accessed [today's date]).

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