Is ACO2 p.Arg424Ser (c.1269_1270delinsAA) pathogenic?

ACO2 p.Arg424Ser (c.12691270delinsAA) is classified Uncertain significance in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-21). Absent from gnomAD.

How common is ACO2 p.Arg424Ser (c.1269_1270delinsAA) in the general population?

ACO2 p.Arg424Ser (c.1269_1270delinsAA) is absent from gnomAD (gnomAD).

ACO2 p.Arg424Ser

c.1269_1270delinsAA · rs2518229799 · VCV2710697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -0.33, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 9,513 bp · p 5.1e-10 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACO2
Protein: p.Arg424Ser
Coding: c.1269_1270delinsAA
MANE Select: NM_001098
dbSNP: rs2518229799
Type: Indel
Location: chr22:41522960 (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.Arg424His Uncertain significance ★★ ⚠ same residue
ACO2 p.Arg424= Likely benign ★★ same residue
ACO2 p.Arg424Cys Uncertain significance ★ ⚠ same residue
ACO2 c.1954-15_1954-14delinsAA Uncertain significance ★★ same type
ACO2 p.Tyr151fs Likely pathogenic ★ same type
ACO2 c.2209-12_2209-11delinsAC Uncertain significance ★ same type
ACO2 c.433-2_433-1delinsTC Uncertain significance ★ same type
ACO2 p.Glu667Leu 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/aco2-p-arg424ser (accessed [today's date]).

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