Is DMD p.Leu460= (c.1378T>C) pathogenic?

DMD p.Leu460= (c.1378T>C) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-20). Rare (popmax 0.136%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Leu460= (c.1378T>C)?

DMD p.Leu460= (c.1378T>C) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Leu460= (c.1378T>C) in the general population?

DMD p.Leu460= (c.1378T>C) is rare (popmax 0.136%, sas) (gnomAD).

DMD p.Leu460=

c.1378T>C · rs746640758 · VCV392072

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.136%, sas)

Conditions

Cardiovascular phenotype

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 3	GERP -0.15, phastCons 0.98
Overall
CADD	7.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% South Asian · 77/56,662 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00647% 78/1,205,347 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.136%	736
Remaining individualsnot grpmax-eligible	0.00211%	47,424

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.Leu460=
Coding: c.1378T>C
MANE Select: NM_004006
dbSNP: rs746640758
Type: single nucleotide variant
Location: chrX:32614407 (GRCh38)

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 Duchenne muscular dystrophy

Similar variants

DMD p.Leu460Phe 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
DMD c.10224-2A>G 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-leu460 (accessed [today's date]).

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