Is DMD p.Arg2951Cys (c.8851C>T) pathogenic?

DMD p.Arg2951Cys (c.8851C>T) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.1283); Very rare (popmax 0.00296%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg2951Cys (c.8851C>T)?

DMD p.Arg2951Cys (c.8851C>T) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg2951Cys (c.8851C>T) in the general population?

DMD p.Arg2951Cys (c.8851C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about DMD p.Arg2951Cys (c.8851C>T)?

AlphaMissense predicts likely benign (score 0.1283) — an in-silico prediction, not a clinical call.

DMD p.Arg2951Cys

c.8851C>T · rs760516307 · VCV222548

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1283	likely benign
REVEL	0.282	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 12	GERP 0.8, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	26.3	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 0.00296% East Asian · 1/33,743 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.0029% 35/1,208,662 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0538%	1,860
Remaining individualsnot grpmax-eligible	0.00631%	15,854
East Asiangrpmax	0.00296%	33,743
African / African-American	0.00176%	56,899
European (non-Finnish)	0.000559%	178,942

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.Arg2951Cys
Coding: c.8851C>T
MANE Select: NM_004006
dbSNP: rs760516307
Type: single nucleotide variant
Location: chrX:31478192 (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

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Arg2951His Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg2951= Likely benign ★ same residue
DMD p.Arg2951fs Likely pathogenic ★ 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

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-arg2951cys (accessed [today's date]).

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