Is LDHA p.Val198= (c.594G>C) pathogenic?

LDHA p.Val198= (c.594G>C) is classified Likely benign in LDHA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0641%, afr); Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

What condition is associated with LDHA p.Val198= (c.594G>C)?

LDHA p.Val198= (c.594G>C) is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

How common is LDHA p.Val198= (c.594G>C) in the general population?

LDHA p.Val198= (c.594G>C) is ultra-rare (popmax 0.0641%, afr) (gnomAD).

LDHA p.Val198=

c.594G>C · rs373534867 · VCV681419

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0641%, afr)

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 0.95
Overall
CADD	9.703	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0641% African / African-American · 47/73,370 alleles

Filtering AF 0.0495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0443%

Overall 0.00319% 49/1,533,844 alleles · ultra-rare exomes 26/1,381,594 · genomes 23/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0641%	1,561
Admixed American	0.00334%	29,955

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.Val198=
Coding: c.594G>C
MANE Select: NM_005566
dbSNP: rs373534867
Type: single nucleotide variant
Location: chr11:18403695 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 46 PDB
Residue 198: 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.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
LDHA p.Ile159Asn Uncertain significance ★★ ⚠ same condition
LDHA p.Lys149Glu 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-val198 (accessed [today's date]).

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