Is ACO2 p.Ala710Asp (c.2129C>A) pathogenic?

ACO2 p.Ala710Asp (c.2129C>A) is classified Uncertain significance in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely benign (0.263); Very rare (popmax 0.00534%, afr).

How common is ACO2 p.Ala710Asp (c.2129C>A) in the general population?

ACO2 p.Ala710Asp (c.2129C>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ACO2 p.Ala710Asp (c.2129C>A)?

AlphaMissense predicts likely benign (score 0.263) — an in-silico prediction, not a clinical call.

ACO2 p.Ala710Asp

c.2129C>A · rs757401683 · VCV2791570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.263	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,296 bp · p 4.7e-05 · regional, not allelic
Overall
CADD	22.4	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 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,092 alleles · very rare

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: ACO2
Protein: p.Ala710Asp
Coding: c.2129C>A
MANE Select: NM_001098
dbSNP: rs757401683
Type: single nucleotide variant
Location: chr22:41527943 (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-ala710asp (accessed [today's date]).

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