KRT6C p.Ala423=
c.1269T>C · VCV3536126
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
Conditions
1
Inborn genetic diseases
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 0.32 | GERP 0.82, phastCons 0.006 |
| Overall | ||
| CADD | 6.281 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,862 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00198%
32/1,613,390 alleles · very rare
exomes 24/1,461,312 · genomes 8/152,078 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00892% | 11,216 |
| African / African-American | 0.00534% | 18,724 |
| Admixed American | 0.005% | 19,999 |
| Finnishnot grpmax-eligible | 0.00469% | 21,344 |
| European (non-Finnish) | 0.00144% | 69,396 |
| South Asian | 0.0011% | 91,066 |
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.Ala423=
- Coding
- c.1269T>C
- MANE Select
- NM_173086
- Type
- single nucleotide variant
- Location
- chr12:52469825 (GRCh38)
- Gene constraint
- LOEUF 1.34 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.63
- Residue 423
- the if rod domain; the 'coil 2' region
Similar variants
- KRT6C p.Arg260Cys Uncertain significance ★★ ⚠ same condition
- KRT6C p.Arg349Trp Uncertain significance ★★ ⚠ same condition
- KRT6C p.Arg466Cys Uncertain significance ★★ ⚠ same condition
- KRT6C p.Asp331His Uncertain significance ★★ ⚠ same condition
- KRT6C p.Glu479Lys Uncertain significance ★★ same condition
- KRT6C p.Gly504Ser Uncertain significance ★★ ⚠ same condition
- KRT6C p.Gly525Ser Uncertain significance ★★ ⚠ same condition
- KRT6C p.Gly57Arg Uncertain significance ★★ ⚠ same condition
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-ala423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown