Is LDHA p.Asp285Val (c.854A>T) pathogenic?

LDHA p.Asp285Val (c.854A>T) is classified Uncertain significance in LDHA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-07-02). AlphaMissense: ambiguous (0.3717); Ultra-rare (popmax 0.0266%, nfe); Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

What condition is associated with LDHA p.Asp285Val (c.854A>T)?

LDHA p.Asp285Val (c.854A>T) is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

How common is LDHA p.Asp285Val (c.854A>T) in the general population?

LDHA p.Asp285Val (c.854A>T) is ultra-rare (popmax 0.0266%, nfe) (gnomAD).

What do computational predictors say about LDHA p.Asp285Val (c.854A>T)?

AlphaMissense predicts ambiguous (score 0.3717) — an in-silico prediction, not a clinical call.

LDHA p.Asp285Val

c.854A>T · rs147520495 · VCV1711317

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0266%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease due to lactate dehydrogenase M-subunit deficiency

Computational evidence

Protein change
AlphaMissense	0.3717	ambiguous
REVEL	0.276	benign-leaning
SaProt	LLR -11.97	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 10 kb · p 5.6e-12 · regional, not allelic
Overall
CADD	24.5	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 0.0266% European (non-Finnish) · 313/1,176,828 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.0207% 333/1,607,264 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0321%	3,113
European (non-Finnish)grpmax	0.0266%	3,760

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LDHA
Protein: p.Asp285Val
Coding: c.854A>T
MANE Select: NM_005566
dbSNP: rs147520495
Type: single nucleotide variant
Location: chr11:18407136 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 46 PDB

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

Disease context

glycogen storage disease due to lactate dehydrogenase M-subunit deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDHA p.Ser137Ter Pathogenic ★★ same condition
LDHA c.*660C>T Uncertain significance ★★ same condition
LDHA p.Arg112Cys Uncertain significance ★★ ⚠ same condition
LDHA p.Arg157His Uncertain significance ★★ ⚠ same condition
LDHA p.Asp46Val Uncertain significance ★★ ⚠ same condition
LDHA p.Ile159Asn Uncertain significance ★★ ⚠ same condition
LDHA p.Lys149Glu Uncertain significance ★★ ⚠ same condition
LDHA p.Ser274Phe Uncertain significance ★★ ⚠ 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/ldha-p-asp285val (accessed [today's date]).

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