Is DLD p.Asn18Ser (c.53A>G) pathogenic?

DLD p.Asn18Ser (c.53A>G) is classified Likely benign in DLD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.0544); Very rare (popmax 0.00593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DLD p.Asn18Ser (c.53A>G)?

DLD p.Asn18Ser (c.53A>G) is associated with Inborn genetic diseases, pyruvate dehydrogenase E3 deficiency (ClinVar).

How common is DLD p.Asn18Ser (c.53A>G) in the general population?

DLD p.Asn18Ser (c.53A>G) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about DLD p.Asn18Ser (c.53A>G)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

DLD p.Asn18Ser

c.53A>G · rs151191365 · VCV2052081

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.9
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	0.733	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

Grpmax group 0.00593% European (non-Finnish) · 70/1,179,722 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00502% 81/1,613,666 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,853
African / African-American	0.00533%	18,762
East Asian	0.00446%	22,433
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0022%	45,496
Finnishnot grpmax-eligible	0.00156%	64,002

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.Asn18Ser
Coding: c.53A>G
MANE Select: NM_000108
dbSNP: rs151191365
Type: single nucleotide variant
Location: chr7:107893213 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB

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 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-asn18ser (accessed [today's date]).

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