KLC2 p.Ala467=
c.1401C>T · rs991860275 · VCV2641985
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -11 | GERP -3.7 |
| Overall | ||
| CADD | 8.453 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,880 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000496%
8/1,613,846 alleles · very rare
exomes 8/1,461,548 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,440 |
| Finnishnot grpmax-eligible | 0.00157% | 63,854 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000339% | 294,989 |
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.Ala467=
- Coding
- c.1401C>T
- MANE Select
- NM_001318734
- dbSNP
- rs991860275
- Type
- single nucleotide variant
- Location
- chr11:66265721 (GRCh38)
- Gene constraint
- LOEUF 0.616 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.79 · 2 PDB
- Residue 467
- an α-helix
Similar variants
- 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
- KLC2 p.Asn170Ser 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-ala467 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown