Is DMD p.Leu268= (c.802T>C) pathogenic?

DMD p.Leu268= (c.802T>C) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.98%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Leu268= (c.802T>C)?

DMD p.Leu268= (c.802T>C) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Leu268= (c.802T>C) in the general population?

DMD p.Leu268= (c.802T>C) is low-frequency (popmax 3.98%, amr) (gnomAD).

DMD p.Leu268=

c.802T>C · rs1800264 · VCV94784

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.98%, 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	all four deltas below 0.2 · A>C here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 2.7, phastCons 0.48
Overall
CADD	6.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.98% Admixed American · 1,812/45,583 alleles

Filtering AF 3.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.76%

Overall 0.233% 2,819/1,208,727 alleles · low-frequency exomes 2,429/1,097,075 · genomes 390/111,652 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.98%	25
East Asian	0.92%	109
South Asian	0.833%	120
Remaining individualsnot grpmax-eligible	0.284%	352
African / African-American	0.0507%	1,974
Finnishnot grpmax-eligible	0.0258%	3,879
Middle Eastern	0.023%	4,345
European (non-Finnish)	0.00526%	19,026

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.Leu268=
Coding: c.802T>C
MANE Select: NM_004006
dbSNP: rs1800264
Type: single nucleotide variant
Location: chrX:32699141 (GRCh38)

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 p.Leu268Ser Uncertain significance ★★ ⚠ same residue
DMD p.Leu268fs Likely pathogenic ★ 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-leu268 (accessed [today's date]).

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