KRT6C p.Arg299=
c.897A>G · rs761041689 · VCV722588
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, 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 -3.6 |
| Overall | ||
| CADD | 8.835 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,864 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000248%
4/1,613,822 alleles · very rare
exomes 2/1,461,720 · genomes 2/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,955 |
| Admixed American | 0.00167% | 60,000 |
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
- KRT6C
- Protein
- p.Arg299=
- Coding
- c.897A>G
- MANE Select
- NM_173086
- dbSNP
- rs761041689
- Type
- single nucleotide variant
- Location
- chr12:52471436 (GRCh38)
- Gene constraint
- LOEUF 1.34 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.63
- Residue 299
- the if rod domain; the 'coil 1b' region
Similar variants
- KRT6C p.Glu472Lys Pathogenic/Likely pathogenic ★★ same type
- KRT6C p.Arg260Cys Uncertain significance ★★ ⚠ same type
- KRT6C p.Arg349Trp Uncertain significance ★★ ⚠ same type
- KRT6C p.Arg466Cys Uncertain significance ★★ ⚠ same type
- KRT6C p.Asp331His Uncertain significance ★★ ⚠ same type
- KRT6C p.Glu479Lys Uncertain significance ★★ same type
- KRT6C p.Gly504Ser Uncertain significance ★★ ⚠ same type
- KRT6C p.Gly525Ser 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/krt6c-p-arg299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown