Is DMD p.Ile407Val (c.1219A>G) pathogenic?

DMD p.Ile407Val (c.1219A>G) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-11). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.00591%, eas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Ile407Val (c.1219A>G)?

DMD p.Ile407Val (c.1219A>G) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ile407Val (c.1219A>G) in the general population?

DMD p.Ile407Val (c.1219A>G) is very rare (popmax 0.00591%, eas) (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.Ile407Val (c.1219A>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

DMD p.Ile407Val

c.1219A>G · rs1463021278 · VCV618066

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00591%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.32	GERP -4.5, phastCons 0.086
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	8.304	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00591% East Asian · 2/33,822 alleles

Filtering AF 0.000979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00033% 4/1,211,114 alleles · very rare exomes 4/1,097,640 · genomes 0/113,474 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00591%	16,911
Remaining individualsnot grpmax-eligible	0.0021%	47,630
South Asian	0.00176%	56,977

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.Ile407Val
Coding: c.1219A>G
MANE Select: NM_004006
dbSNP: rs1463021278
Type: single nucleotide variant
Location: chrX:32644244 (GRCh38)
Residue 407: an α-helix

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.Ile407Thr Uncertain significance ★★ ⚠ 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-ile407val (accessed [today's date]).

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