DLD c.267+12T>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
Conditions
1
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 +12 | near-intronic (+12 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.55, phastCons 0.93 |
| Non-coding constraint | Z -0.86 | 1 kb window · o/e 1.07 · regional · uncalibrated |
| Overall | ||
| CADD | 11.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,178,958 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,612,786 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+12T>C
- MANE Select
- NM_000108
- dbSNP
- rs377312138
- Type
- single nucleotide variant
- Location
- chr7:107902405 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.69 · 17 PDB
Disease context
pyruvate dehydrogenase E3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 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-267-plus-12t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown