Is ENO3 p.Ser263= (c.789G>A) pathogenic?

ENO3 p.Ser263= (c.789G>A) is classified Benign in ENO3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.57%, afr); Associated with glycogen storage disease due to muscle beta-enolase deficiency.

What condition is associated with ENO3 p.Ser263= (c.789G>A)?

ENO3 p.Ser263= (c.789G>A) is associated with glycogen storage disease due to muscle beta-enolase deficiency (ClinVar).

How common is ENO3 p.Ser263= (c.789G>A) in the general population?

ENO3 p.Ser263= (c.789G>A) is low-frequency (popmax 2.57%, afr) (gnomAD).

ENO3 p.Ser263=

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.789G>A · rs75748087 · VCV324145

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.57%, afr)

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 -2.4	GERP -3.7
Overall
CADD	1.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.57% African / African-American · 1,930/75,048 alleles

Filtering AF 2.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.44%

Overall 0.142% 2,287/1,614,190 alleles · low-frequency exomes 1,126/1,461,890 · genomes 1,161/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.57%	39
Admixed American	0.363%	275
Remaining individualsnot grpmax-eligible	0.157%	638
Middle Eastern	0.099%	1,010
South Asian	0.00329%	30,361
European (non-Finnish)	0.00263%	38,066
East Asian	0.00223%	44,876

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.Ser263=
Coding: c.789G>A
MANE Select: NM_053013
dbSNP: rs75748087
Type: single nucleotide variant
Location: chr17:4955528 (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 263: a modified residue (phosphoserine)

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.Ser263Leu Uncertain significance ★★ same residue
ENO3 p.Ser263dup 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

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-ser263 (accessed [today's date]).

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