Is LDHA p.Asp46= (c.138T>C) pathogenic?

LDHA p.Asp46= (c.138T>C) is classified Likely benign in LDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-19). Absent from gnomAD v4.1; Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

How common is LDHA p.Asp46= (c.138T>C) in the general population?

LDHA p.Asp46= (c.138T>C) is absent from gnomAD v4.1 (gnomAD).

LDHA p.Asp46=

Q: What condition is associated with LDHA p.Asp46= (c.138T>C)?

LDHA p.Asp46= (c.138T>C) is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

c.138T>C · rs2134021527 · VCV1100956

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 5	GERP 1.9, phastCons 1
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LDHA
Protein: p.Asp46=
Coding: c.138T>C
MANE Select: NM_005566
dbSNP: rs2134021527
Type: single nucleotide variant
Location: chr11:18399442 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 46 PDB
Residue 46: a binding site; 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.Asp46Val Uncertain significance ★★ ⚠ same residue
LDHA p.Asp46Leu 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.Ile159Asn 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-asp46 (accessed [today's date]).

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