Is LDHA c.710+1del pathogenic?

LDHA c.710+1del is classified Likely pathogenic in LDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). Ultra-rare (popmax 0.01%, amr); Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

How common is LDHA c.710+1del in the general population?

LDHA c.710+1del is ultra-rare (popmax 0.01%, amr) (gnomAD).

LDHA c.710+1del

Q: What condition is associated with LDHA c.710+1del?

LDHA c.710+1del is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

VCV3599453

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Non-coding constraint	Z 0.99	1 kb window · o/e 0.89 · regional · uncalibrated

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,908 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.000515% 7/1,359,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,985
European (non-Finnish)	9.2e-05%	1,086,568

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
Coding: c.710+1del
MANE Select: NM_005566
Type: Deletion
Location: chr11:18403811 (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 c.126+3_126+6del Uncertain significance ★★ same condition
LDHA c.593-1del Likely pathogenic ★ same condition
LDHA c.711-13del Likely benign ★ same condition
LDHA c.835-14_835-11del Likely benign ★ same condition
LDHA p.Phe332_Ter333insTer Likely benign ★ same condition
LDHA p.Leu254fs Pathogenic same condition
LDHA p.Glu229fs Pathogenic/Likely pathogenic ★★ same condition
LDHA p.Leu214fs Pathogenic/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/ldha-c-710-plus-1del (accessed [today's date]).

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