KLC2 p.Arg554=
c.1662G>A · rs367871112 · VCV1638838
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00517%, 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 3.8 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 11.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00517%
European (non-Finnish) · 61/1,179,868 alleles
Filtering AF
0.0041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00372%
Overall
0.00409%
66/1,613,520 alleles · very rare
exomes 58/1,461,312 · genomes 8/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00517% | 19,342 |
| Finnishnot grpmax-eligible | 0.00469% | 21,301 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,227 |
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.Arg554=
- Coding
- c.1662G>A
- MANE Select
- NM_001318734
- dbSNP
- rs367871112
- Type
- single nucleotide variant
- Location
- chr11:66266152 (GRCh38)
- Gene constraint
- LOEUF 0.616 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.79 · 2 PDB
Similar variants
- KLC2 p.Arg554Lys 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-arg554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown