Is DMD p.Cys816Phe (c.2447G>T) pathogenic?

DMD p.Cys816Phe (c.2447G>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-30). AlphaMissense: ambiguous (0.3886); Absent from gnomAD v4.1; Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Cys816Phe (c.2447G>T)?

DMD p.Cys816Phe (c.2447G>T) is associated with Duchenne muscular dystrophy, Becker muscular dystrophy, dilated cardiomyopathy 3B (ClinVar).

How common is DMD p.Cys816Phe (c.2447G>T) in the general population?

DMD p.Cys816Phe (c.2447G>T) is absent from gnomAD v4.1 (gnomAD).

How is Duchenne 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.Cys816Phe (c.2447G>T)?

AlphaMissense predicts ambiguous (score 0.3886) — an in-silico prediction, not a clinical call.

DMD p.Cys816Phe

c.2447G>T · VCV3378158

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3886 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.3886	ambiguous
REVEL	0.371	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.4	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.Cys816Phe
Coding: c.2447G>T
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32491452 (GRCh38)

Full DMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Becker muscular dystrophy dilated cardiomyopathy 3B

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Cys816Ter Pathogenic ★ same residue
DMD p.Cys816fs Pathogenic/Likely pathogenic ★★ same residue
DMD p.Cys816= Likely benign ★ 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-cys816phe (accessed [today's date]).

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