Is DMD p.Leu212Val (c.634C>G) pathogenic?

DMD p.Leu212Val (c.634C>G) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: ambiguous (0.4755); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Leu212Val (c.634C>G)?

DMD p.Leu212Val (c.634C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Leu212Val (c.634C>G) in the general population?

DMD p.Leu212Val (c.634C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Leu212Val (c.634C>G)?

AlphaMissense predicts ambiguous (score 0.4755) — an in-silico prediction, not a clinical call.

DMD p.Leu212Val

c.634C>G · VCV3840486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4755	ambiguous
REVEL	0.833	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Leu212Val
Coding: c.634C>G
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32809508 (GRCh38)
Residue 212: the calponin-homology (ch) 2 domain; the 'actin-binding' region

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 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
DMD c.9974+1G>A Pathogenic/Likely pathogenic ★★ same condition
DMD p.Arg3034Ter Pathogenic ★★ same condition
DMD p.Gln1144= 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-leu212val (accessed [today's date]).

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