Is DMD p.Val505Leu (c.1513G>C) pathogenic?

DMD p.Val505Leu (c.1513G>C) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2637); Rare (popmax 0.254%, mid); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Val505Leu (c.1513G>C)?

DMD p.Val505Leu (c.1513G>C) is associated with Cardiovascular phenotype, intellectual disability, cardiomyopathy (ClinVar).

How common is DMD p.Val505Leu (c.1513G>C) in the general population?

DMD p.Val505Leu (c.1513G>C) is rare (popmax 0.254%, mid) (gnomAD).

What do computational predictors say about DMD p.Val505Leu (c.1513G>C)?

AlphaMissense predicts likely benign (score 0.2637) — an in-silico prediction, not a clinical call.

DMD p.Val505Leu

c.1513G>C · rs140340626 · VCV94471

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

AlphaMissense

likely benign

0.2637 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.254%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2637	likely benign
REVEL	0.089	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	22.5	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 0.254% Middle Eastern · 11/4,332 alleles

Filtering AF 0.174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.155% 1,854/1,197,840 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.28%	358
Middle Easterngrpmax	0.254%	394
European (non-Finnish)	0.181%	552
Remaining individualsnot grpmax-eligible	0.144%	695
Admixed American	0.0678%	1,475
African / African-American	0.0158%	6,336
South Asian	0.00531%	18,841

Finnish 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.Val505Leu
Coding: c.1513G>C
MANE Select: NM_004006
dbSNP: rs140340626
Type: single nucleotide variant
Location: chrX:32595846 (GRCh38)
Residue 505: 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: intellectual disability cardiomyopathy restrictive cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy mitochondrial disease

Similar variants

DMD p.Val505Asp 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-val505leu (accessed [today's date]).

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