KLC2 p.Ser436=
c.1308C>T · rs147513948 · VCV774626
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.774%, mid)
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 4 | GERP 0.76, phastCons 1 |
| Overall | ||
| CADD | 20.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.774%
Middle Eastern · 43/5,556 alleles
Filtering AF
0.591%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.526%
Overall
0.375%
5,675/1,514,820 alleles · rare
exomes 5,289/1,364,754 · genomes 386/150,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.774% | 129 |
| Finnishnot grpmax-eligible | 0.583% | 172 |
| European (non-Finnish) | 0.426% | 235 |
| Remaining individualsnot grpmax-eligible | 0.306% | 327 |
| South Asian | 0.295% | 340 |
| Ashkenazi Jewishnot grpmax-eligible | 0.204% | 490 |
| Admixed American | 0.0679% | 1,473 |
| African / African-American | 0.0579% | 1,726 |
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.Ser436=
- Coding
- c.1308C>T
- MANE Select
- NM_001318734
- dbSNP
- rs147513948
- Type
- single nucleotide variant
- Location
- chr11:66265209 (GRCh38)
- Gene constraint
- LOEUF 0.616 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.79 · 2 PDB
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-ser436 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown