Is DLAT p.Thr231= (c.693C>T) pathogenic?

DLAT p.Thr231= (c.693C>T) is classified Benign in DLAT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Common (popmax 8.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Thr231= (c.693C>T)?

DLAT p.Thr231= (c.693C>T) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How is Pyruvate dehydrogenase deficiency inherited?

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

DLAT p.Thr231=

Q: How common is DLAT p.Thr231= (c.693C>T) in the general population?

DLAT p.Thr231= (c.693C>T) is common (popmax 8.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.693C>T · rs34680691 · VCV137091

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 8.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

pyruvate dehydrogenase E2 deficiency

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 0.58	GERP 0.72, phastCons 1
Overall
CADD	9.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.8% African / African-American · 6,601/74,974 alleles

Filtering AF 8.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.55%

Overall 0.482% 7,773/1,613,858 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.8%	11
Remaining individualsnot grpmax-eligible	0.706%	142
Admixed American	0.599%	167
Middle Eastern	0.577%	173
South Asian	0.0406%	2,461
European (non-Finnish)	0.0249%	4,013
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,790
Finnishnot grpmax-eligible	0.00625%	16,005

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: DLAT
Protein: p.Thr231=
Coding: c.693C>T
MANE Select: NM_001931
dbSNP: rs34680691
Type: single nucleotide variant
Location: chr11:112033436 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 231: the lipoyl-binding 2 domain; a β-strand

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

Disease context

pyruvate dehydrogenase E2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pyruvate dehydrogenase deficiency (Orphanet):

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

Similar variants

DLAT c.976-1G>A Pathogenic/Likely pathogenic ★★ same condition
DLAT p.Arg435Ter Pathogenic ★★ same condition
DLAT p.Glu138Ter Pathogenic ★★ same condition
DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT c.1130-6T>G Uncertain significance ★★ same condition
DLAT p.Ala109Thr Uncertain significance ★★ ⚠ same condition
DLAT p.Ala191Gly Uncertain significance ★★ ⚠ same condition
DLAT p.Ala191Val Uncertain significance ★★ ⚠ 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/dlat-p-thr231 (accessed [today's date]).

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