Is DLD p.Arg482fs (c.1446_1447del) pathogenic?

DLD p.Arg482fs (c.14461447del) is classified Pathogenic in DLD (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-09). Very rare (popmax 8.48e-05%, nfe); Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.Arg482fs (c.1446_1447del)?

DLD p.Arg482fs (c.1446_1447del) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Arg482fs (c.1446_1447del) in the general population?

DLD p.Arg482fs (c.1446_1447del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Maple syrup urine disease inherited?

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

DLD p.Arg482fs

c.1446_1447del · rs1554400713 · VCV551065

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

pyruvate dehydrogenase E3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (13 of 14, 20 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.071	GERP -4.2, phastCons 0.35

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,792 alleles

Overall 6.84e-05% 1/1,461,552 alleles · very rare

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: DLD
Protein: p.Arg482fs
Coding: c.1446_1447del
MANE Select: NM_000108
dbSNP: rs1554400713
Type: Microsatellite
Location: chr7:107919079 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 482: an α-helix; a UniProt-annotated variant site (in dldd; reduced enzyme activity)

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 p.Arg482Gly Pathogenic same residue
DLD p.Asp448fs Pathogenic/Likely pathogenic ★★ same condition
DLD p.His96fs Pathogenic/Likely pathogenic ★★ same condition
DLD c.337+4_337+7del Likely pathogenic ★ same condition
DLD p.His396fs Likely pathogenic ★ same condition
DLD p.Leu76fs Likely pathogenic ★ same condition
DLD p.Tyr8fs Likely pathogenic ★ same condition
DLD c.685-8_685-5del Likely benign ★ 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-arg482fs (accessed [today's date]).

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