KRT6B p.Pro154=
c.462C>T · rs145409385 · VCV3052217
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
Conditions
1
KRT6B-related disorder
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 -1.1 | GERP -0.27 |
| Overall | ||
| CADD | 12.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,862 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00223%
36/1,613,076 alleles · ultra-rare
exomes 32/1,461,788 · genomes 4/151,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,409 |
| Admixed American | 0.005% | 19,997 |
| South Asian | 0.00439% | 22,756 |
| African / African-American | 0.0027% | 37,057 |
| European (non-Finnish) | 0.00161% | 62,104 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
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.Pro154=
- Coding
- c.462C>T
- MANE Select
- NM_005555
- dbSNP
- rs145409385
- Type
- single nucleotide variant
- Location
- chr12:52451617 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.76
- Residue 154
- the 'head' region
Disease context
KRT6B-related disorder
Similar variants
- KRT6B p.Gly66= Likely benign same condition
- KRT6B p.Gly88Arg Benign same condition
- KRT6B p.Leu61= Likely benign same condition
- KRT6B p.Pro128= Benign same condition
- KRT6B p.Ser60= Likely benign same condition
- KRT6B p.Ser67= Likely benign same condition
- KRT6B p.Asn172del Pathogenic ★★ same condition
- KRT6B p.Glu461Lys Pathogenic/Likely pathogenic ★★ 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-pro154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown