Is LDHA p.Val270= (c.810G>A) pathogenic?

LDHA p.Val270= (c.810G>A) is classified Conflicting classifications of pathogenicity in LDHA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0165%, mid); Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

What condition is associated with LDHA p.Val270= (c.810G>A)?

LDHA p.Val270= (c.810G>A) is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

How common is LDHA p.Val270= (c.810G>A) in the general population?

LDHA p.Val270= (c.810G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LDHA p.Val270=

c.810G>A · rs187005834 · VCV2195924

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

glycogen storage disease due to lactate dehydrogenase M-subunit 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 0.24	GERP -3.8, phastCons 0.93
Overall
CADD	5.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00273% 44/1,613,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Admixed American	0.0117%	8,573
South Asian	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0048%	20,831
East Asian	0.00223%	44,856
European (non-Finnish)	0.00212%	47,193
Finnishnot grpmax-eligible	0.00156%	64,018

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.Val270=
Coding: c.810G>A
MANE Select: NM_005566
dbSNP: rs187005834
Type: single nucleotide variant
Location: chr11:18405548 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 46 PDB
Residue 270: a β-strand

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.Val270Ala Uncertain significance ★ ⚠ same residue
LDHA p.Val270Leu Uncertain significance ★ ⚠ same residue
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.Asp285Val Uncertain significance ★★ ⚠ same condition
LDHA p.Asp46Val 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-val270 (accessed [today's date]).

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