Is DLAT p.Ala43Val (c.128C>T) pathogenic?

DLAT p.Ala43Val (c.128C>T) is classified Benign in DLAT (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0735); Common (popmax 56.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Ala43Val (c.128C>T)?

DLAT p.Ala43Val (c.128C>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.

What do computational predictors say about DLAT p.Ala43Val (c.128C>T)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

DLAT p.Ala43Val

Q: How common is DLAT p.Ala43Val (c.128C>T) in the general population?

DLAT p.Ala43Val (c.128C>T) is common (popmax 56.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.128C>T · rs2303436 · VCV128897

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 56.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pyruvate dehydrogenase E2 deficiency

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -3.7
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	9.188	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.9% East Asian · 25,508/44,858 alleles

Filtering AF 56.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 56%

Overall 36.3% 585,302/1,613,720 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	56.9%	2
Amishnot grpmax-eligible	55.2%	2
Finnishnot grpmax-eligible	42.7%	2
South Asian	40.1%	2
Admixed American	38.5%	3
Middle Eastern	36%	3
European (non-Finnish)	35.8%	3
Remaining individualsnot grpmax-eligible	35.7%	3
Ashkenazi Jewishnot grpmax-eligible	28.5%	4
African / African-American	22.3%	4

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.Ala43Val
Coding: c.128C>T
MANE Select: NM_001931
dbSNP: rs2303436
Type: single nucleotide variant
Location: chr11:112025600 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 43: a UniProt-annotated variant site (in); the 'disordered' region

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-ala43val (accessed [today's date]).

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