Is DLAT p.Asp283fs (c.848_849del) pathogenic?

DLAT p.Asp283fs (c.848849del) is classified Pathogenic/Likely pathogenic in DLAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-21). Very rare (popmax 0.000169%, nfe); Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Asp283fs (c.848_849del)?

DLAT p.Asp283fs (c.848_849del) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Asp283fs (c.848_849del) in the general population?

DLAT p.Asp283fs (c.848_849del) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Pyruvate dehydrogenase deficiency inherited?

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

DLAT p.Asp283fs

c.848_849del · rs782704553 · VCV434944

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

pyruvate dehydrogenase E2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,834 alleles · very rare

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.Asp283fs
Coding: c.848_849del
MANE Select: NM_001931
dbSNP: rs782704553
Type: Deletion
Location: chr11:112037333 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 283: 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 p.Thr322_Pro325del Uncertain significance ★★ same condition
DLAT c.381+22delT Benign/Likely benign ★★ same condition
DLAT p.Cys344fs Likely pathogenic ★ same condition
DLAT p.Glu268fs Pathogenic ★ same condition
DLAT p.Ile159fs Likely pathogenic ★ same condition
DLAT c.976-2del Conflicting classifications of pathogenicity ★ same condition
DLAT p.Glu115del Uncertain significance ★ same condition
DLAT c.1677+21_1677+24del Likely benign ★ 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-asp283fs (accessed [today's date]).

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