Is DLAT p.Val608Glu (c.1823T>A) pathogenic?

DLAT p.Val608Glu (c.1823T>A) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.5401); Absent from gnomAD v4.1; Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Val608Glu (c.1823T>A)?

DLAT p.Val608Glu (c.1823T>A) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Val608Glu (c.1823T>A) in the general population?

DLAT p.Val608Glu (c.1823T>A) is absent from gnomAD v4.1 (gnomAD).

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.Val608Glu (c.1823T>A)?

AlphaMissense predicts ambiguous (score 0.5401) — an in-silico prediction, not a clinical call.

DLAT p.Val608Glu

c.1823T>A · rs2498718723 · VCV1717122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pyruvate dehydrogenase E2 deficiency

Computational evidence

Protein change
AlphaMissense	0.5401	ambiguous
REVEL	0.303	indeterminate
SaProt	LLR -12.74	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLAT
Protein: p.Val608Glu
Coding: c.1823T>A
MANE Select: NM_001931
dbSNP: rs2498718723
Type: single nucleotide variant
Location: chr11:112062414 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 608: 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-val608glu (accessed [today's date]).

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