Is DLAT p.Val242fs (c.723dup) pathogenic?

DLAT p.Val242fs (c.723dup) is classified Pathogenic in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 0.0011%, sas); Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Val242fs (c.723dup)?

DLAT p.Val242fs (c.723dup) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Val242fs (c.723dup) in the general population?

DLAT p.Val242fs (c.723dup) is very rare (popmax 0.0011%, sas) (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.Val242fs

c.723dup · rs782029228 · VCV2778456

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 5 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 0.0011% South Asian · 1/91,024 alleles

Overall 0.000137% 2/1,461,164 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,024
European (non-Finnish)	8.48e-05%	1,179,505

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.Val242fs
Coding: c.723dup
MANE Select: NM_001931
dbSNP: rs782029228
Type: Duplication
Location: chr11:112033458 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 242: the lipoyl-binding 2 domain

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.Asn602_Glu603insAsp Uncertain significance ★ same condition
DLAT p.Pro197_Ala198insGlnAlaAlaProAlaProThrPro Uncertain significance ★ same condition
DLAT c.1515-13dup Benign ★ same condition
DLAT c.279+18dup Benign ★ same condition
DLAT c.976-1G>A Pathogenic/Likely pathogenic ★★ same condition
DLAT p.Arg435Ter Pathogenic ★★ same condition
DLAT p.Asp283fs Pathogenic/Likely pathogenic ★★ same condition
DLAT p.Glu138Ter 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/dlat-p-val242fs (accessed [today's date]).

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