FASTKD2 p.Pro566=
c.1698G>A · rs151258385 · VCV1403062
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
combined oxidative phosphorylation deficiency 44
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -2.1 |
| Overall | ||
| CADD | 0.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00192%
31/1,613,720 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| East Asian | 0.0134% | 7,476 |
| Admixed American | 0.00333% | 29,995 |
| African / African-American | 0.00267% | 37,497 |
| European (non-Finnish) | 0.00161% | 62,094 |
| South Asian | 0.0011% | 91,064 |
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
- FASTKD2
- Protein
- p.Pro566=
- Coding
- c.1698G>A
- MANE Select
- NM_001136193
- dbSNP
- rs151258385
- Type
- single nucleotide variant
- Location
- chr2:206788040 (GRCh38)
- Gene constraint
- LOEUF 1.203 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.39
- Residue 566
- a UniProt-annotated variant site (in coxpd44; decreased mitochondrial large ribosomal subunit assembly); a UniProt-annotated variant site (in coxpd44)
Similar variants
- FASTKD2 p.Pro566Leu Uncertain significance ★ ⚠ same residue
- FASTKD2 c.882-1G>A Pathogenic/Likely pathogenic ★★ same condition
- FASTKD2 c.991-2A>G Likely pathogenic ★★ same condition
- FASTKD2 p.Arg290Ter Pathogenic ★★ same condition
- FASTKD2 p.Arg358Ter Pathogenic/Likely pathogenic ★★ same condition
- FASTKD2 p.Arg432Ter Pathogenic/Likely pathogenic ★★ same condition
- FASTKD2 p.Cys283Ter Pathogenic/Likely pathogenic ★★ same condition
- FASTKD2 p.Gln564Ter Pathogenic/Likely pathogenic ★★ same condition
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/fastkd2-p-pro566 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown