Is ENO3 p.Val85= (c.255G>A) pathogenic?

ENO3 p.Val85= (c.255G>A) is classified Likely benign in ENO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-15). Very rare (popmax 0.000339%, nfe); Associated with glycogen storage disease due to muscle beta-enolase deficiency.

What condition is associated with ENO3 p.Val85= (c.255G>A)?

ENO3 p.Val85= (c.255G>A) is associated with glycogen storage disease due to muscle beta-enolase deficiency (ClinVar).

How common is ENO3 p.Val85= (c.255G>A) in the general population?

ENO3 p.Val85= (c.255G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

ENO3 p.Val85=

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.255G>A · rs200608211 · VCV2049570

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, 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 7.3	GERP 0.68, phastCons 1
Overall
CADD	10.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,982 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,132 alleles · very rare exomes 1/1,461,828 · genomes 3/152,304 · 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.Val85=
Coding: c.255G>A
MANE Select: NM_053013
dbSNP: rs200608211
Type: single nucleotide variant
Location: chr17:4953286 (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 85: a UniProt-annotated variant site (in)

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 p.Val85Ala Benign/Likely benign ★★ same residue
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

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-val85 (accessed [today's date]).

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