Is ENO2 p.Arg183Gln (c.548G>A) pathogenic?

ENO2 p.Arg183Gln (c.548G>A) is classified Uncertain significance in ENO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.033%, mid).

How common is ENO2 p.Arg183Gln (c.548G>A) in the general population?

ENO2 p.Arg183Gln (c.548G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ENO2 p.Arg183Gln (c.548G>A)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

ENO2 p.Arg183Gln

c.548G>A · rs781786493 · VCV3088899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP -0.17, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 6,964 bp · p 3.6e-09 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000547% 8/1,461,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
East Asian	0.00446%	22,437
European (non-Finnish)	0.000339%	295,002

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: ENO2
Protein: p.Arg183Gln
Coding: c.548G>A
MANE Select: NM_001975
dbSNP: rs781786493
Type: single nucleotide variant
Location: chr12:6918043 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 97.14 · 16 PDB
Residue 183: an α-helix

Full ENO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENO2 p.Ala27Asp Uncertain significance ★ ⚠ same type
ENO2 p.Ala331Thr Uncertain significance ★ ⚠ same type
ENO2 p.Arg126Trp Uncertain significance ★ ⚠ same type
ENO2 p.Arg179Gln Uncertain significance ★ ⚠ same type
ENO2 p.Arg269Gln Uncertain significance ★ ⚠ same type
ENO2 p.Arg269Leu Uncertain significance ★ ⚠ same type
ENO2 p.Arg327His Uncertain significance ★ ⚠ same type
ENO2 p.Arg32Gln Uncertain significance ★ ⚠ same type

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/eno2-p-arg183gln (accessed [today's date]).

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