Is ACO2 p.Gly601Asp (c.1802G>A) pathogenic?

ACO2 p.Gly601Asp (c.1802G>A) is classified Conflicting classifications of pathogenicity in ACO2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1.

How common is ACO2 p.Gly601Asp (c.1802G>A) in the general population?

ACO2 p.Gly601Asp (c.1802G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACO2 p.Gly601Asp (c.1802G>A)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

ACO2 p.Gly601Asp

c.1802G>A · rs863223881 · VCV214024

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic
REVEL	0.594	indeterminate
SaProt	LLR -16.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 1,015 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	32.0	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

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: ACO2
Protein: p.Gly601Asp
Coding: c.1802G>A
MANE Select: NM_001018050 · reported on NM_001098
dbSNP: rs863223881
Type: single nucleotide variant
Location: chr22:41526302 (GRCh38)

Full ACO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/aco2-p-gly601asp (accessed [today's date]).

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