KRT12 p.Arg164=
c.492A>G · VCV4935091
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
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 -0.006 | GERP -2.6 |
| Overall | ||
| CADD | 8.636 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,180,032 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00149%
24/1,614,232 alleles · very rare
exomes 24/1,461,886 · genomes 0/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00195% | 51,306 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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
- KRT12
- Protein
- p.Arg164=
- Coding
- c.492A>G
- MANE Select
- NM_000223
- Type
- single nucleotide variant
- Location
- chr17:40866695 (GRCh38)
- Gene constraint
- LOEUF 0.979 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.57
- Residue 164
- the if rod domain; the 'linker 1' region
Similar variants
- KRT12 p.Met129Val Pathogenic/Likely pathogenic ★★ same type
- KRT12 p.Asp213Tyr Uncertain significance ★★ ⚠ same type
- KRT12 p.Gln486Glu Uncertain significance ★★ ⚠ same type
- KRT12 p.Ile195Phe Uncertain significance ★★ ⚠ same type
- KRT12 p.Val228Ile Uncertain significance ★★ ⚠ same type
- KRT12 c.808-17T>A Benign/Likely benign ★★ same type
- KRT12 p.Arg20Trp Benign ★★ ⚠ same type
- KRT12 p.Gln475Arg Likely benign ★★ ⚠ 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/krt12-p-arg164 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown