Is DLD p.Ser506Leu (c.1517C>T) pathogenic?

DLD p.Ser506Leu (c.1517C>T) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.7488); Absent from gnomAD v4.1; Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.Ser506Leu (c.1517C>T)?

DLD p.Ser506Leu (c.1517C>T) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Ser506Leu (c.1517C>T) in the general population?

DLD p.Ser506Leu (c.1517C>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.

What do computational predictors say about DLD p.Ser506Leu (c.1517C>T)?

AlphaMissense predicts likely pathogenic (score 0.7488) — an in-silico prediction, not a clinical call.

DLD p.Ser506Leu

c.1517C>T · rs1382247182 · VCV2797384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7488 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pyruvate dehydrogenase E3 deficiency

Computational evidence

Protein change
AlphaMissense	0.7488	likely pathogenic
REVEL	0.152	moderately benign-leaning
SaProt	LLR -14.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	23.6	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

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.Ser506Leu
Coding: c.1517C>T
MANE Select: NM_000108
dbSNP: rs1382247182
Type: single nucleotide variant
Location: chr7:107919246 (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-ser506leu (accessed [today's date]).

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