Is DLD p.Thr240= (c.720A>G) pathogenic?

DLD p.Thr240= (c.720A>G) is classified Likely benign in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-16). Very rare (popmax 0.0011%, sas); Associated with pyruvate dehydrogenase E3 deficiency.

What condition is associated with DLD p.Thr240= (c.720A>G)?

DLD p.Thr240= (c.720A>G) is associated with pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Thr240= (c.720A>G) in the general population?

DLD p.Thr240= (c.720A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Maple syrup urine disease inherited?

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

DLD p.Thr240=

c.720A>G · rs1165243466 · VCV2797587

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

pyruvate dehydrogenase E3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -1.7, phastCons 0.99
Overall
CADD	7.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.000424%	235,983

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.Thr240=
Coding: c.720A>G
MANE Select: NM_000108
dbSNP: rs1165243466
Type: single nucleotide variant
Location: chr7:107915541 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 240: 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 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-p-thr240 (accessed [today's date]).

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