Is DLAT p.Glu19Gln (c.55G>C) pathogenic?

DLAT p.Glu19Gln (c.55G>C) is classified Benign/Likely benign in DLAT (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0834); Low-frequency (popmax 2.5%, mid); Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Glu19Gln (c.55G>C)?

DLAT p.Glu19Gln (c.55G>C) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Glu19Gln (c.55G>C) in the general population?

DLAT p.Glu19Gln (c.55G>C) is low-frequency (popmax 2.5%, mid) (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.Glu19Gln (c.55G>C)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

DLAT p.Glu19Gln

c.55G>C · rs61757217 · VCV137086

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.5%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pyruvate dehydrogenase E2 deficiency

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -4.88	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 0.29	GERP -4.1, phastCons 0.004
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	9.396	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 2.5% Middle Eastern · 151/6,052 alleles

Filtering AF 2.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.05%

Overall 0.827% 13,356/1,614,048 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.5%	40
Ashkenazi Jewishnot grpmax-eligible	1.02%	98
Admixed American	0.993%	101
European (non-Finnish)	0.943%	106
Remaining individualsnot grpmax-eligible	0.859%	116
Finnishnot grpmax-eligible	0.394%	254
South Asian	0.303%	330
African / African-American	0.148%	676
East Asian	0.00669%	14,959

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.Glu19Gln
Coding: c.55G>C
MANE Select: NM_001931
dbSNP: rs61757217
Type: single nucleotide variant
Location: chr11:112025527 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB

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-glu19gln (accessed [today's date]).

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