Is DLD p.His396fs (c.1187_1188del) pathogenic?

DLD p.His396fs (c.11871188del) is classified Likely pathogenic in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Absent from gnomAD; Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.His396fs (c.1187_1188del)?

DLD p.His396fs (c.1187_1188del) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.His396fs (c.1187_1188del) in the general population?

DLD p.His396fs (c.1187_1188del) is absent from gnomAD (gnomAD).

How is Maple syrup urine disease inherited?

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

DLD p.His396fs

c.1187_1188del · rs2535602632 · VCV1726989

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 11 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DLD
Protein: p.His396fs
Coding: c.1187_1188del
MANE Select: NM_000108
dbSNP: rs2535602632
Type: Microsatellite
Location: chr7:107917407 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 396: a β-strand

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.Leu76fs Likely pathogenic ★ same condition
DLD p.Tyr8fs Likely pathogenic ★ same condition
DLD c.685-8_685-5del Likely benign ★ same condition
DLD p.Ile507fs 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-p-his396fs (accessed [today's date]).

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