Is DMD p.Leu44= (c.132A>G) pathogenic?

DMD p.Leu44= (c.132A>G) is classified Likely benign in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-28). Very rare (popmax 0.00403%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Leu44= (c.132A>G)?

DMD p.Leu44= (c.132A>G) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Leu44= (c.132A>G) in the general population?

DMD p.Leu44= (c.132A>G) is very rare (popmax 0.00403%, nfe) (gnomAD).

DMD p.Leu44=

c.132A>G · rs1316036563 · VCV1118016

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00403%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.21	GERP -1.4, phastCons 0.3
Overall
CADD	7.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00403% European (non-Finnish) · 36/894,124 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.00306% 37/1,209,760 alleles · very rare exomes 37/1,096,670 · genomes 0/113,090 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00403%	24,837
Remaining individualsnot grpmax-eligible	0.0021%	47,574

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.Leu44=
Coding: c.132A>G
MANE Select: NM_004006
dbSNP: rs1316036563
Type: single nucleotide variant
Location: chrX:32849782 (GRCh38)
Residue 44: the calponin-homology (ch) 1 domain; a turn; 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

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

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Leu44fs Pathogenic ★ same residue
DMD p.Leu44Pro Uncertain significance ★ ⚠ 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-leu44 (accessed [today's date]).

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