Is DMD p.Leu40= (c.120C>T) pathogenic?

DMD p.Leu40= (c.120C>T) is classified Likely benign in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-16). Very rare (popmax 8.29e-05%); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Leu40= (c.120C>T)?

DMD p.Leu40= (c.120C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Leu40= (c.120C>T) in the general population?

DMD p.Leu40= (c.120C>T) is very rare (popmax 8.29e-05%) (gnomAD).

DMD p.Leu40=

c.120C>T · rs1214971151 · VCV1749811

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.29e-05%)

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 3.8	GERP -0.2, phastCons 1
Overall
CADD	11.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.29e-05%

Overall 8.29e-05% 1/1,205,883 alleles · very rare exomes 0/1,095,661 · genomes 1/110,222 · joint denominator

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.Leu40=
Coding: c.120C>T
MANE Select: NM_004006
dbSNP: rs1214971151
Type: single nucleotide variant
Location: chrX:32849794 (GRCh38)
Residue 40: 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

Similar variants

DMD p.Leu40His Uncertain significance ★ ⚠ same residue
DMD p.Leu40Phe Uncertain significance ★ ⚠ same residue
DMD p.Leu40Val Uncertain significance ★ ⚠ same residue
DMD c.2804-2A>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.31+1G>C Pathogenic ★★ same condition
DMD c.3432+2036A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.3433-1G>A Pathogenic ★★ same condition
DMD c.357+1G>T 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-leu40 (accessed [today's date]).

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