Is DMD p.Pro705Leu (c.2114C>T) pathogenic?

DMD p.Pro705Leu (c.2114C>T) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-19). AlphaMissense: likely benign (0.1058); Very rare (popmax 0.00296%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Pro705Leu (c.2114C>T)?

DMD p.Pro705Leu (c.2114C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Pro705Leu (c.2114C>T) in the general population?

DMD p.Pro705Leu (c.2114C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about DMD p.Pro705Leu (c.2114C>T)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

DMD p.Pro705Leu

c.2114C>T · VCV4842488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.356	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,807 alleles

Overall 8.26e-05% 1/1,210,668 alleles · very rare exomes 1/1,097,214 · genomes 0/113,454 · 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.Pro705Leu
Coding: c.2114C>T
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32545213 (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

Similar variants

DMD p.Pro705Arg Uncertain significance ★ same residue
DMD p.Pro705Gln 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
DMD c.9974+1G>A Pathogenic/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-pro705leu (accessed [today's date]).

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