Is ENO2 p.Ala27Asp (c.80C>A) pathogenic?

ENO2 p.Ala27Asp (c.80C>A) is classified Uncertain significance in ENO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1074); Absent from gnomAD v4.1.

How common is ENO2 p.Ala27Asp (c.80C>A) in the general population?

ENO2 p.Ala27Asp (c.80C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENO2 p.Ala27Asp (c.80C>A)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

ENO2 p.Ala27Asp

c.80C>A · VCV4018044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.88, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 6,964 bp · p 3.6e-09 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: ENO2
Protein: p.Ala27Asp
Coding: c.80C>A
MANE Select: NM_001975
Type: single nucleotide variant
Location: chr12:6915912 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 97.14 · 16 PDB

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

Similar variants

ENO2 p.Ala331Thr Uncertain significance ★ ⚠ same type
ENO2 p.Arg126Trp Uncertain significance ★ ⚠ same type
ENO2 p.Arg179Gln Uncertain significance ★ ⚠ same type
ENO2 p.Arg183Gln 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-ala27asp (accessed [today's date]).

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