Is DLD p.Ala501Val (c.1502C>T) pathogenic?

DLD p.Ala501Val (c.1502C>T) is classified Uncertain significance in DLD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-24). AlphaMissense: likely benign (0.2477); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with DLD p.Ala501Val (c.1502C>T)?

DLD p.Ala501Val (c.1502C>T) is associated with Inborn genetic diseases, pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Ala501Val (c.1502C>T) in the general population?

DLD p.Ala501Val (c.1502C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DLD p.Ala501Val (c.1502C>T)?

AlphaMissense predicts likely benign (score 0.2477) — an in-silico prediction, not a clinical call.

DLD p.Ala501Val

c.1502C>T · rs527263746 · VCV2158829

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2477 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2477	likely benign
REVEL	0.577	indeterminate
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00112% 18/1,612,468 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
East Asian	0.00223%	44,838
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	0.0011%	90,718
South Asian	0.0011%	90,924

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.Ala501Val
Coding: c.1502C>T
MANE Select: NM_000108
dbSNP: rs527263746
Type: single nucleotide variant
Location: chr7:107919231 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 501: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pyruvate dehydrogenase E3 deficiency

Similar variants

DLD p.Ala501= Conflicting classifications of pathogenicity ★ 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-ala501val (accessed [today's date]).

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