Is DMD p.Lys138= (c.414G>A) pathogenic?

DMD p.Lys138= (c.414G>A) is classified Likely benign in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0109%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Lys138= (c.414G>A)?

DMD p.Lys138= (c.414G>A) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Lys138= (c.414G>A) in the general population?

DMD p.Lys138= (c.414G>A) is ultra-rare (popmax 0.0109%, amr) (gnomAD).

DMD p.Lys138=

c.414G>A · rs1299509319 · VCV1146395

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 2.4, phastCons 1
Overall
CADD	11.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% Admixed American · 5/45,701 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00272%

Overall 0.000496% 6/1,209,938 alleles · ultra-rare exomes 5/1,098,013 · genomes 1/111,925 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0109%	9,140
Remaining individualsnot grpmax-eligible	0.0021%	47,585

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.Lys138=
Coding: c.414G>A
MANE Select: NM_004006
dbSNP: rs1299509319
Type: single nucleotide variant
Location: chrX:32816584 (GRCh38)
Residue 138: an α-helix; the calponin-homology (ch) 2 domain; the 'actin-binding' 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: Duchenne muscular dystrophy

Similar variants

DMD p.Lys138Asn Uncertain significance ★ same residue
DMD p.Lys138Glu 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

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-lys138 (accessed [today's date]).

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