KRT14 p.Ile412=
c.1236C>T · VCV4750403
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00237%, 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 -0.44 | GERP -0.34, phastCons 0.002 |
| Overall | ||
| CADD | 12.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00237%
European (non-Finnish) · 28/1,179,998 alleles
Filtering AF
0.00164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00142%
Overall
0.0018%
29/1,613,416 alleles · very rare
exomes 24/1,461,306 · genomes 5/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00237% | 42,143 |
| East Asian | 0.00223% | 44,874 |
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
- KRT14
- Protein
- p.Ile412=
- Coding
- c.1236C>T
- MANE Select
- NM_000526
- Type
- single nucleotide variant
- Location
- chr17:41583273 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.00 · 6 PDB
- Residue 412
- the if rod domain; a UniProt-annotated variant site (in ebs1c; uncertain significance); the 'coil 2' region; an α-helix
Similar variants
- KRT14 p.Ile412Thr Pathogenic ★ same residue
- KRT14 c.526-2A>C Likely pathogenic ★★ same type
- KRT14 c.927+1G>A Pathogenic ★★ same type
- KRT14 p.Arg125Cys Pathogenic ★★ same type
- KRT14 p.Arg125His Pathogenic ★★ same type
- KRT14 p.Arg125Leu Pathogenic ★★ same type
- KRT14 p.Arg288Leu Pathogenic/Likely pathogenic ★★ same type
- KRT14 p.Arg388Cys 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/krt14-p-ile412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown