KLC2 p.Pro593=
c.1779G>A · VCV3706085
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00322%, nfe)
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 -0.35 | GERP -2.1, phastCons 0.001 |
| Overall | ||
| CADD | 7.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,179,852 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00266%
43/1,613,702 alleles · very rare
exomes 41/1,461,528 · genomes 2/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,049 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| East Asian | 0.00223% | 44,880 |
| Admixed American | 0.00167% | 59,990 |
| South Asian | 0.0011% | 91,042 |
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
- KLC2
- Protein
- p.Pro593=
- Coding
- c.1779G>A
- MANE Select
- NM_001318734
- Type
- single nucleotide variant
- Location
- chr11:66266484 (GRCh38)
- Gene constraint
- LOEUF 0.616 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.79 · 2 PDB
- Residue 593
- the 'disordered' region
Similar variants
- KLC2 p.Pro593Leu Uncertain significance ★ ⚠ same residue
- KLC2 p.Arg110His Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg418Gln Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg418Trp Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg479His Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg509Gln Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg616Gln Uncertain significance ★★ ⚠ same type
- KLC2 p.Arg96Gln 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/klc2-p-pro593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown