Is ACO2 p.Val556fs (c.1666del) pathogenic?

ACO2 p.Val556fs (c.1666del) is classified Pathogenic in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Absent from gnomAD.

How common is ACO2 p.Val556fs (c.1666del) in the general population?

ACO2 p.Val556fs (c.1666del) is absent from gnomAD (gnomAD).

ACO2 p.Val556fs

c.1666del · rs2066570950 · VCV1454488

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 14 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.6	GERP -3.7, phastCons 0.001

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.Val556fs
Coding: c.1666del
MANE Select: NM_001098
dbSNP: rs2066570950
Type: Deletion
Location: chr22:41525253 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 95.44
Residue 556: the 'disordered' region

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

Similar variants

ACO2 p.Val556Leu Uncertain significance ★★ ⚠ 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-val556fs (accessed [today's date]).

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