Is DLD c.*28G>T pathogenic?

DLD c.28G>T is classified Benign in DLD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2021-07-01). Common (popmax 50.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Leigh syndrome.

What condition is associated with DLD c.*28G>T?

DLD c.*28G>T is associated with Leigh syndrome, pyruvate dehydrogenase E3 deficiency, pyruvate dehydrogenase deficiency (ClinVar).

How is Leigh syndrome inherited?

Typically Autosomal recessive, Mitochondrial inheritance (Orphanet). A genetic counselor can assess individual risk for a family.

DLD c.*28G>T

Q: How common is DLD c.*28G>T in the general population?

DLD c.*28G>T is common (popmax 50.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs17154615 · VCV358573

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 50.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Leigh syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.2, phastCons 1
Non-coding constraint	Z 1.73	1 kb window · o/e 0.83 · regional · uncalibrated
Overall
CADD	12.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.1% East Asian · 22,273/44,420 alleles

Filtering AF 49.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.4%

Overall 13.3% 208,351/1,561,314 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	50.1%	2
South Asian	20.9%	5
Finnishnot grpmax-eligible	17.3%	6
Remaining individualsnot grpmax-eligible	14.4%	7
Admixed American	14.3%	7
Middle Eastern	14.2%	7
Ashkenazi Jewishnot grpmax-eligible	13.7%	7
European (non-Finnish)	11.7%	9
Amishnot grpmax-eligible	9.21%	11
African / African-American	2.31%	43

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: DLD
Coding: c.*28G>T
MANE Select: NM_000108
dbSNP: rs17154615
Type: single nucleotide variant
Location: chr7:107919287 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB

Full DLD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leigh syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pyruvate dehydrogenase E3 deficiency pyruvate dehydrogenase deficiency

For Leigh syndrome (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance, X-linked recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DLD c.1464+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLD c.198+1G>T Likely pathogenic ★★ same condition
DLD c.39+1G>A Likely pathogenic ★★ same condition
DLD c.40-2A>G Likely pathogenic ★★ same condition
DLD c.583-1G>C Likely pathogenic ★★ same condition
DLD c.684+1G>T Likely pathogenic ★★ same condition
DLD c.875+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLD p.Arg315Ter 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/dld-c-star-28g-t (accessed [today's date]).

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