Is ENO3 p.Ala2= (c.6C>T) pathogenic?

ENO3 p.Ala2= (c.6C>T) is classified Likely benign in ENO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Very rare (popmax 0.000254%, nfe); Associated with glycogen storage disease due to muscle beta-enolase deficiency.

What condition is associated with ENO3 p.Ala2= (c.6C>T)?

ENO3 p.Ala2= (c.6C>T) is associated with glycogen storage disease due to muscle beta-enolase deficiency (ClinVar).

How common is ENO3 p.Ala2= (c.6C>T) in the general population?

ENO3 p.Ala2= (c.6C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

ENO3 p.Ala2=

Q: How is Glycogen storage disease due to muscle beta-enolase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.6C>T · rs1174736563 · VCV2420050

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

glycogen storage disease due to muscle beta-enolase 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 1.9	GERP -0.38, phastCons 1
Overall
CADD	14.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,972 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,986 alleles · very rare exomes 2/1,461,792 · genomes 1/152,194 · joint denominator

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: ENO3
Protein: p.Ala2=
Coding: c.6C>T
MANE Select: NM_053013
dbSNP: rs1174736563
Type: single nucleotide variant
Location: chr17:4951835 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.63 · 1 PDB
Residue 2: a modified residue (n-acetylalanine)

Full ENO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to muscle beta-enolase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to muscle beta-enolase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

ENO3 c.1067+1G>A Uncertain significance ★★ same condition
ENO3 p.Ala159Pro Uncertain significance ★★ ⚠ same condition
ENO3 p.Ala39Thr Uncertain significance ★★ ⚠ same condition
ENO3 p.Arg183Cys Uncertain significance ★★ ⚠ same condition
ENO3 p.Arg253His Uncertain significance ★★ ⚠ same condition
ENO3 p.Arg269Gln Uncertain significance ★★ ⚠ same condition
ENO3 p.Arg30Ter Uncertain significance ★★ same condition
ENO3 p.Arg32Gln 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/eno3-p-ala2 (accessed [today's date]).

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