Is DLAT p.Cys59= (c.177C>T) pathogenic?

DLAT p.Cys59= (c.177C>T) is classified Likely benign in DLAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-20). Ultra-rare (popmax 0.0254%, afr); Associated with pyruvate dehydrogenase E2 deficiency.

What condition is associated with DLAT p.Cys59= (c.177C>T)?

DLAT p.Cys59= (c.177C>T) is associated with pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Cys59= (c.177C>T) in the general population?

DLAT p.Cys59= (c.177C>T) is ultra-rare (popmax 0.0254%, afr) (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.Cys59=

c.177C>T · rs150994149 · VCV512662

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Conditions

pyruvate dehydrogenase E2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.37	GERP -4.4, phastCons 0.001
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,908 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00155% 25/1,613,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,943
Admixed American	0.00667%	14,998
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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.Cys59=
Coding: c.177C>T
MANE Select: NM_001931
dbSNP: rs150994149
Type: single nucleotide variant
Location: chr11:112025649 (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-cys59 (accessed [today's date]).

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