Is DLD c.337+17T>C pathogenic?

DLD c.337+17T>C is classified Likely benign in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). Ultra-rare (popmax 0.0159%, eas); Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD c.337+17T>C?

DLD c.337+17T>C is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD c.337+17T>C in the general population?

DLD c.337+17T>C is ultra-rare (popmax 0.0159%, eas) (gnomAD).

How is Maple syrup urine disease inherited?

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

DLD c.337+17T>C

rs1428305327 · VCV2911551

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

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 +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 0.98
Non-coding constraint	Z 0.16	1 kb window · o/e 0.99 · regional · uncalibrated
Overall
CADD	15.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% East Asian · 7/44,016 alleles

Filtering AF 0.00738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00523%

Overall 0.000606% 9/1,484,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,288
European (non-Finnish)	0.000188%	532,127

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.337+17T>C
MANE Select: NM_000108
dbSNP: rs1428305327
Type: single nucleotide variant
Location: chr7:107903564 (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-c-337-plus-17t-c (accessed [today's date]).

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