Is DMD p.Leu57Pro (c.170T>C) pathogenic?

DMD p.Leu57Pro (c.170T>C) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-23). AlphaMissense: likely pathogenic (0.968); No allele count reported in gnomAD v4.1 (AN 1,206,060); Associated with Becker muscular dystrophy.

What condition is associated with DMD p.Leu57Pro (c.170T>C)?

DMD p.Leu57Pro (c.170T>C) is associated with Becker muscular dystrophy (ClinVar).

How common is DMD p.Leu57Pro (c.170T>C) in the general population?

DMD p.Leu57Pro (c.170T>C) is no allele count reported in gnomAD v4.1 (AN 1,206,060) (gnomAD).

How is Becker muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Leu57Pro (c.170T>C)?

AlphaMissense predicts likely pathogenic (score 0.968) — an in-silico prediction, not a clinical call.

DMD p.Leu57Pro

c.170T>C · rs886044431 · VCV290352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.968 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,206,060)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Becker muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.968	likely pathogenic · top 7% in DMD
REVEL	0.943	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,206,060). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DMD
Protein: p.Leu57Pro
Coding: c.170T>C
MANE Select: NM_004006
dbSNP: rs886044431
Type: single nucleotide variant
Location: chrX:32849744 (GRCh38)
Residue 57: the calponin-homology (ch) 1 domain; an α-helix; 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

Becker muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Becker muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DMD p.Leu57Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Leu57= Likely benign ★ same residue
DMD c.10921+2T>C Likely pathogenic ★★ same condition
DMD c.1704+1G>T Pathogenic ★★ same condition
DMD c.1705-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.1812+1G>A Pathogenic/Likely pathogenic ★★ same condition
DMD c.2623-2A>G Pathogenic ★★ same condition
DMD c.2804-1G>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-leu57pro (accessed [today's date]).

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