Is DLAT p.Ser391Ile (c.1171_1172delinsAT) pathogenic?

DLAT p.Ser391Ile (c.11711172delinsAT) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Absent from gnomAD; Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Ser391Ile (c.1171_1172delinsAT)?

DLAT p.Ser391Ile (c.1171_1172delinsAT) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Ser391Ile (c.1171_1172delinsAT) in the general population?

DLAT p.Ser391Ile (c.1171_1172delinsAT) is absent from gnomAD (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.Ser391Ile

c.1171_1172delinsAT · rs2498529234 · VCV2092683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DLAT
Protein: p.Ser391Ile
Coding: c.1171_1172delinsAT
MANE Select: NM_001931
dbSNP: rs2498529234
Type: Indel
Location: chr11:112043507 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 391: the peripheral subunit-binding (psbd) 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 c.975+15_975+16delinsGT Likely 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
DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT c.1130-6T>G Uncertain significance ★★ same condition
DLAT p.Ala109Thr 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-ser391ile (accessed [today's date]).

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