Is DLD c.267+15del pathogenic?

DLD c.267+15del is classified Benign in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-06). Very rare (popmax 0.00133%, afr); Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD c.267+15del?

DLD c.267+15del is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD c.267+15del in the general population?

DLD c.267+15del is very rare (popmax 0.00133%, afr) (gnomAD).

How is Maple syrup urine disease inherited?

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

DLD c.267+15del

rs886061906 · VCV358567

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

pyruvate dehydrogenase E3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +15	near-intronic (+15 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.17	GERP -3.5
Non-coding constraint	Z -0.86	1 kb window · o/e 1.07 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,012 alleles

Overall 6.85e-05% 1/1,460,550 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
Coding: c.267+15del
MANE Select: NM_000108
dbSNP: rs886061906
Type: Deletion
Location: chr7:107902405 (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.Gln268fs Pathogenic/Likely pathogenic ★★ same condition
DLD p.Gly137del Pathogenic/Likely pathogenic ★★ same condition
DLD p.Gly246fs Likely pathogenic ★★ same condition
DLD p.Thr34_Tyr35insTer Pathogenic/Likely pathogenic ★★ same condition
DLD p.Tyr473fs Pathogenic ★★ same condition
DLD p.Asp121fs Pathogenic ★ same condition
DLD p.Asp286fs Likely pathogenic ★ same condition
DLD p.Asp368fs 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-c-267-plus-15del (accessed [today's date]).

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