Is DMD p.Phe296Leu (c.888C>A) pathogenic?

DMD p.Phe296Leu (c.888C>A) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely pathogenic (0.9091); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 3B.

What condition is associated with DMD p.Phe296Leu (c.888C>A)?

DMD p.Phe296Leu (c.888C>A) is associated with dilated cardiomyopathy 3B, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Phe296Leu (c.888C>A) in the general population?

DMD p.Phe296Leu (c.888C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Phe296Leu (c.888C>A)?

AlphaMissense predicts likely pathogenic (score 0.9091) — an in-silico prediction, not a clinical call.

DMD p.Phe296Leu

c.888C>A · rs977310228 · VCV1199257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9091 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,207,076)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

dilated cardiomyopathy 3B

Computational evidence

Protein change
AlphaMissense	0.9091	likely pathogenic
REVEL	0.041	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.33, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	19.69	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

No allele count reported in gnomAD v4.1 (AN 1,207,076). 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.Phe296Leu
Coding: c.888C>A
MANE Select: NM_004006
dbSNP: rs977310228
Type: single nucleotide variant
Location: chrX:32697942 (GRCh38)

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

Disease context

dilated cardiomyopathy 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Phe296= 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
DMD c.10224-2A>G 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-phe296leu (accessed [today's date]).

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