Is DLD p.Ile507fs (c.1520_1523del) pathogenic?

DLD p.Ile507fs (c.15201523del) is classified Likely pathogenic in DLD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-10-12). Very rare (popmax 0.000254%, nfe); Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.Ile507fs (c.1520_1523del)?

DLD p.Ile507fs (c.1520_1523del) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Ile507fs (c.1520_1523del) in the general population?

DLD p.Ile507fs (c.1520_1523del) is very rare (popmax 0.000254%, 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.Ile507fs

c.1520_1523del · rs777884525 · VCV371542

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,080 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,459,690 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.Ile507fs
Coding: c.1520_1523del
MANE Select: NM_000108
dbSNP: rs777884525
Type: Microsatellite
Location: chr7:107919243 (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 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.Arg482fs 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-ile507fs (accessed [today's date]).

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