Is LDHA p.Pro154Ser (c.460C>T) pathogenic?

LDHA p.Pro154Ser (c.460C>T) is classified Uncertain significance in LDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-24). AlphaMissense: ambiguous (0.4108); Absent from gnomAD v4.1; Associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.

What condition is associated with LDHA p.Pro154Ser (c.460C>T)?

LDHA p.Pro154Ser (c.460C>T) is associated with glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ClinVar).

How common is LDHA p.Pro154Ser (c.460C>T) in the general population?

LDHA p.Pro154Ser (c.460C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LDHA p.Pro154Ser (c.460C>T)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

LDHA p.Pro154Ser

c.460C>T · rs2134028222 · VCV1978568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

glycogen storage disease due to lactate dehydrogenase M-subunit deficiency

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 10 kb · p 5.6e-12 · regional, not allelic
Overall
CADD	27.4	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

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.Pro154Ser
Coding: c.460C>T
MANE Select: NM_005566
dbSNP: rs2134028222
Type: single nucleotide variant
Location: chr11:18402881 (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.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-pro154ser (accessed [today's date]).

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