KRT6B p.Asp273=
c.819T>C · rs150034493 · VCV776704
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.64%, afr)
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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.279 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.64%
African / African-American · 1,233/74,980 alleles
Filtering AF
1.57%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.54%
Overall
0.096%
1,550/1,613,894 alleles · low-frequency
exomes 794/1,461,618 · genomes 756/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.64% | 61 |
| Ashkenazi Jewishnot grpmax-eligible | 0.193% | 519 |
| Admixed American | 0.162% | 619 |
| Remaining individualsnot grpmax-eligible | 0.147% | 679 |
| Middle Eastern | 0.0495% | 2,019 |
| European (non-Finnish) | 0.00525% | 19,030 |
| East Asian | 0.00446% | 22,434 |
| South Asian | 0.00439% | 22,769 |
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.Asp273=
- Coding
- c.819T>C
- MANE Select
- NM_005555
- dbSNP
- rs150034493
- Type
- single nucleotide variant
- Location
- chr12:52449851 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.76
- Residue 273
- the if rod domain; the 'coil 1b' region
Similar variants
- KRT6B p.Asp273Gly Uncertain significance ★ ⚠ same residue
- 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
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-asp273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown