Is DMD p.Phe1388Val (c.4162T>G) pathogenic?

DMD p.Phe1388Val (c.4162T>G) is classified Benign in DMD (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.048); Common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Phe1388Val (c.4162T>G)?

DMD p.Phe1388Val (c.4162T>G) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

What do computational predictors say about DMD p.Phe1388Val (c.4162T>G)?

AlphaMissense predicts likely benign (score 0.048) — an in-silico prediction, not a clinical call.

DMD p.Phe1388Val

Q: How common is DMD p.Phe1388Val (c.4162T>G) in the general population?

DMD p.Phe1388Val (c.4162T>G) is common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4162T>G · rs28715870 · VCV94615

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

AlphaMissense

likely benign

0.048 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.048	likely benign
REVEL	0.024	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 4.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	12.98	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 8.6% African / African-American · 4,904/57,009 alleles

Filtering AF 8.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.32%

Overall 0.498% 6,017/1,208,952 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.6%	12
Admixed American	0.835%	120
Remaining individualsnot grpmax-eligible	0.738%	136
Middle Eastern	0.505%	198
Ashkenazi Jewishnot grpmax-eligible	0.154%	648
South Asian	0.13%	767
European (non-Finnish)	0.0281%	3,565

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.Phe1388Val
Coding: c.4162T>G
MANE Select: NM_004006
dbSNP: rs28715870
Type: single nucleotide variant
Location: chrX:32411823 (GRCh38)
Residue 1388: a UniProt-annotated variant site (in)

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 dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

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
DMD c.10554-2A>G Pathogenic/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-phe1388val (accessed [today's date]).

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