Is DLD p.Asp479Val (c.1436A>T) pathogenic?

DLD p.Asp479Val (c.1436A>T) is classified Pathogenic/Likely pathogenic in DLD (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.9916); Absent from gnomAD v4.1; Associated with DLD-related disorder.

What condition is associated with DLD p.Asp479Val (c.1436A>T)?

DLD p.Asp479Val (c.1436A>T) is associated with DLD-related disorder, lactic acidosis, pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Asp479Val (c.1436A>T) in the general population?

DLD p.Asp479Val (c.1436A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLD p.Asp479Val (c.1436A>T)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

DLD p.Asp479Val

c.1436A>T · rs397514649 · VCV40186

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLD-related disorder

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic ✓ concordant with ClinVar · top 10% in DLD
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -15.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.76 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLD
Protein: p.Asp479Val
Coding: c.1436A>T
MANE Select: NM_000108
dbSNP: rs397514649
Type: single nucleotide variant
Location: chr7:107919071 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 479: an α-helix; a UniProt-annotated variant site (in dldd; reduced dehydrogenase activity; increased proteolytic activity)

Full DLD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLD-related disorder

Also linked: lactic acidosis pyruvate dehydrogenase E3 deficiency

Similar variants

DLD p.Asp479= Likely benign ★ same residue
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

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-asp479val (accessed [today's date]).

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