Is DMD p.Phe1458Tyr (c.4373T>A) pathogenic?

DMD p.Phe1458Tyr (c.4373T>A) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1475); Rare (popmax 0.112%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Phe1458Tyr (c.4373T>A)?

DMD p.Phe1458Tyr (c.4373T>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Phe1458Tyr (c.4373T>A) in the general population?

DMD p.Phe1458Tyr (c.4373T>A) is rare (popmax 0.112%, amr) (gnomAD).

What do computational predictors say about DMD p.Phe1458Tyr (c.4373T>A)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

DMD p.Phe1458Tyr

c.4373T>A · rs777274879 · VCV618604

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.141	moderately 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 11	GERP 2.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.3	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 0.112% Admixed American · 51/45,664 alleles

Filtering AF 0.0872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0785%

Overall 0.00422% 51/1,208,984 alleles · rare

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.Phe1458Tyr
Coding: c.4373T>A
MANE Select: NM_004006
dbSNP: rs777274879
Type: single nucleotide variant
Location: chrX:32389646 (GRCh38)
Residue 1458: the 'interaction with synm' region

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: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Phe1458= 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-phe1458tyr (accessed [today's date]).

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