KRT6B p.Ser516=
c.1548C>T · rs61749468 · VCV778593
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.11%, afr)
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 -1.2 | GERP -1.6 |
| Overall | ||
| CADD | 9.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.11%
African / African-American · 3,084/75,060 alleles
Filtering AF
3.99%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.94%
Overall
0.228%
3,674/1,614,058 alleles · low-frequency
exomes 1,919/1,461,696 · genomes 1,755/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.11% | 24 |
| Middle Eastern | 0.314% | 319 |
| Admixed American | 0.285% | 351 |
| Remaining individualsnot grpmax-eligible | 0.27% | 370 |
| European (non-Finnish) | 0.0184% | 5,437 |
| South Asian | 0.0154% | 6,506 |
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
- KRT6B
- Protein
- p.Ser516=
- Coding
- c.1548C>T
- MANE Select
- NM_005555
- dbSNP
- rs61749468
- Type
- single nucleotide variant
- Location
- chr12:52447337 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.76
- Residue 516
- the 'tail' region
Similar variants
- KRT6B p.Glu461Lys Pathogenic/Likely pathogenic ★★ same type
- KRT6B p.Glu472Lys Pathogenic ★★ same type
- KRT6B p.Ala403Val Uncertain significance ★★ ⚠ same type
- KRT6B p.Arg260His Uncertain significance ★★ same type
- KRT6B p.Arg375His Uncertain significance ★★ ⚠ same type
- KRT6B p.Arg386His Uncertain significance ★★ same type
- KRT6B p.Gln208His Uncertain significance ★★ ⚠ same type
- KRT6B p.Gln379Arg 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/krt6b-p-ser516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown