FASTKD2 p.Leu499=
c.1495T>C · rs781715702 · VCV3023075
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -2.9 |
| Overall | ||
| CADD | 0.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,870 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000372%
6/1,613,648 alleles · very rare
exomes 6/1,461,294 · genomes 0/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,870 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.000339% | 294,883 |
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.Leu499=
- Coding
- c.1495T>C
- MANE Select
- NM_001136193
- dbSNP
- rs781715702
- Type
- single nucleotide variant
- Location
- chr2:206786800 (GRCh38)
- Gene constraint
- LOEUF 1.203 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.39
- Residue 499
- a UniProt-annotated variant site (in coxpd44; decreased mitochondrial large ribosomal subunit assembly); a UniProt-annotated variant site (in coxpd44)
Similar variants
- FASTKD2 p.Leu499Ser Uncertain significance ★ ⚠ same residue
- FASTKD2 c.882-1G>A Pathogenic/Likely pathogenic ★★ same type
- FASTKD2 c.991-2A>G Likely pathogenic ★★ same type
- FASTKD2 p.Arg290Ter Pathogenic ★★ same type
- FASTKD2 p.Arg358Ter Pathogenic/Likely pathogenic ★★ same type
- FASTKD2 p.Arg432Ter Pathogenic/Likely pathogenic ★★ same type
- FASTKD2 p.Cys283Ter Pathogenic/Likely pathogenic ★★ same type
- FASTKD2 p.Gln564Ter Pathogenic/Likely 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/fastkd2-p-leu499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown