Is ACO2 p.Arg92Gln (c.275G>A) pathogenic?

ACO2 p.Arg92Gln (c.275G>A) is classified Uncertain significance in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2359); Very rare (popmax 0.00668%, eas).

How common is ACO2 p.Arg92Gln (c.275G>A) in the general population?

ACO2 p.Arg92Gln (c.275G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about ACO2 p.Arg92Gln (c.275G>A)?

AlphaMissense predicts likely benign (score 0.2359) — an in-silico prediction, not a clinical call.

ACO2 p.Arg92Gln

c.275G>A · rs147763800 · VCV950038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2359	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -11.71	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 7.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 7,916 bp · p 5e-15 · regional, not allelic
Overall
CADD	26.1	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 0.00668% East Asian · 3/44,904 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00198% 32/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,968
African / African-American	0.004%	24,982
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00186%	53,639

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.Arg92Gln
Coding: c.275G>A
MANE Select: NM_001098
dbSNP: rs147763800
Type: single nucleotide variant
Location: chr22:41507892 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 95.44

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

Similar variants

ACO2 p.Arg92Pro Uncertain significance ★ ⚠ same residue
ACO2 p.Arg92Trp Uncertain significance ★ ⚠ same residue
ACO2 p.Arg92_Pro93insLeuArg Uncertain significance ★ same residue
ACO2 p.Arg378Ter Pathogenic/Likely pathogenic ★★ same type
ACO2 p.Arg58Ter Pathogenic/Likely pathogenic ★★ same type
ACO2 p.Arg84Ter Pathogenic ★★ same type
ACO2 p.Glu464Ter Pathogenic/Likely pathogenic ★★ same type
ACO2 p.Gly503Ter Pathogenic ★★ 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/aco2-p-arg92gln (accessed [today's date]).

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