Is DLD p.Val83= (c.249T>C) pathogenic?

DLD p.Val83= (c.249T>C) is classified Benign in DLD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.14%, afr); Associated with pyruvate dehydrogenase deficiency.

What condition is associated with DLD p.Val83= (c.249T>C)?

DLD p.Val83= (c.249T>C) is associated with pyruvate dehydrogenase deficiency, pyruvate dehydrogenase E3 deficiency, Leigh syndrome (ClinVar).

How common is DLD p.Val83= (c.249T>C) in the general population?

DLD p.Val83= (c.249T>C) is low-frequency (popmax 3.14%, afr) (gnomAD).

How is Pyruvate dehydrogenase deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

DLD p.Val83=

c.249T>C · rs2228664 · VCV137092

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.14%, afr)

Conditions

pyruvate dehydrogenase deficiency

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 · T>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -1.9, phastCons 1
Overall
CADD	9.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.14% African / African-American · 2,355/75,024 alleles

Filtering AF 3.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.99%

Overall 0.164% 2,643/1,613,914 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.14%	32
Admixed American	0.198%	504
Remaining individualsnot grpmax-eligible	0.181%	553
Middle Eastern	0.149%	673
South Asian	0.00659%	15,179
European (non-Finnish)	0.00339%	29,497
East Asian	0.00223%	44,808

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
Protein: p.Val83=
Coding: c.249T>C
MANE Select: NM_000108
dbSNP: rs2228664
Type: single nucleotide variant
Location: chr7:107902375 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 83: a disulfide bond; an α-helix

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

Disease context

pyruvate dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pyruvate dehydrogenase E3 deficiency Leigh syndrome

For Pyruvate dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable, X-linked dominant
Onset: Childhood, Infancy, Neonatal

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-p-val83 (accessed [today's date]).

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