Is DLD p.Ile195= (c.585A>T) pathogenic?

DLD p.Ile195= (c.585A>T) is classified Likely benign in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). Absent from gnomAD v4.1; Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.Ile195= (c.585A>T)?

DLD p.Ile195= (c.585A>T) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Ile195= (c.585A>T) in the general population?

DLD p.Ile195= (c.585A>T) is absent from gnomAD v4.1 (gnomAD).

How is Maple syrup urine disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DLD p.Ile195=

c.585A>T · rs2032004224 · VCV2804075

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pyruvate dehydrogenase E3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.61	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.066	GERP -0.63, phastCons 0.89
Overall
CADD	13.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLD
Protein: p.Ile195=
Coding: c.585A>T
MANE Select: NM_000108
dbSNP: rs2032004224
Type: single nucleotide variant
Location: chr7:107906269 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB

Full DLD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pyruvate dehydrogenase E3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

DLD c.1464+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLD c.198+1G>T Likely pathogenic ★★ same condition
DLD c.39+1G>A Likely pathogenic ★★ same condition
DLD c.40-2A>G Likely pathogenic ★★ same condition
DLD c.583-1G>C Likely pathogenic ★★ same condition
DLD c.684+1G>T Likely pathogenic ★★ same condition
DLD c.875+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLD p.Arg315Ter Likely 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/dld-p-ile195 (accessed [today's date]).

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