Is DLAT p.Arg44= (c.132T>G) pathogenic?

DLAT p.Arg44= (c.132T>G) is classified Likely benign in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Very rare (popmax 0.00966%, nfe); Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Arg44= (c.132T>G)?

DLAT p.Arg44= (c.132T>G) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Arg44= (c.132T>G) in the general population?

DLAT p.Arg44= (c.132T>G) is very rare (popmax 0.00966%, 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.Arg44=

c.132T>G · VCV3705645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00966%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.63	GERP -4.1
Overall
CADD	4.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00966% European (non-Finnish) · 114/1,179,992 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00725% 117/1,613,810 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00966%	10,351
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00133%	74,932

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.Arg44=
Coding: c.132T>G
MANE Select: NM_001931
Type: single nucleotide variant
Location: chr11:112025604 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 44: the 'disordered' region

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.Arg44Leu Uncertain significance ★ ⚠ same residue
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

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-arg44 (accessed [today's date]).

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