Is ACO2 p.Asp512fs (c.1534_1537del) pathogenic?

ACO2 p.Asp512fs (c.15341537del) is classified Pathogenic in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Absent from gnomAD.

How common is ACO2 p.Asp512fs (c.1534_1537del) in the general population?

ACO2 p.Asp512fs (c.1534_1537del) is absent from gnomAD (gnomAD).

ACO2 p.Asp512fs

c.1534_1537del · rs2146139092 · VCV1391740

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 13 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.4	GERP -3.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Asp512fs
Coding: c.1534_1537del
MANE Select: NM_001098
dbSNP: rs2146139092
Type: Deletion
Location: chr22:41524897 (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.Asp512Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ACO2 p.Gln702fs Pathogenic ★★ same type
ACO2 p.Lys520fs Pathogenic/Likely pathogenic ★★ same type
ACO2 p.Ser614del Uncertain significance ★★ same type
ACO2 c.1953+17del Likely benign ★★ same type
ACO2 p.Ala675fs Pathogenic ★ same type
ACO2 p.Arg656fs Pathogenic ★ same type
ACO2 p.Asn317_Leu318insTer 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-asp512fs (accessed [today's date]).

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