Is DMD p.Phe2099Ser (c.6296T>C) pathogenic?

DMD p.Phe2099Ser (c.6296T>C) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.8783); Very rare (popmax 0.00175%, afr); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Phe2099Ser (c.6296T>C)?

DMD p.Phe2099Ser (c.6296T>C) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Phe2099Ser (c.6296T>C) in the general population?

DMD p.Phe2099Ser (c.6296T>C) is very rare (popmax 0.00175%, afr) (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.Phe2099Ser (c.6296T>C)?

AlphaMissense predicts likely pathogenic (score 0.8783) — an in-silico prediction, not a clinical call.

DMD p.Phe2099Ser

c.6296T>C · rs1229763776 · VCV1038956

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.8783	likely pathogenic
REVEL	0.418	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	23.9	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 0.00175% African / African-American · 1/57,081 alleles

Overall 8.28e-05% 1/1,207,296 alleles · very rare exomes 0/1,095,666 · genomes 1/111,630 · 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.Phe2099Ser
Coding: c.6296T>C
MANE Select: NM_004006
dbSNP: rs1229763776
Type: single nucleotide variant
Location: chrX:32217058 (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: cardiomyopathy Becker muscular dystrophy

For Duchenne muscular dystrophy (Orphanet):

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

Similar variants

DMD p.Phe2099Val Uncertain significance ★ same residue
DMD p.Phe2099= 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
DMD c.10223+1G>C 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-phe2099ser (accessed [today's date]).

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