KRT14 p.Arg407=
c.1219C>A · rs149217449 · VCV784356
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.6%, 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 0.62 | GERP 0.77, phastCons 0.06 |
| Overall | ||
| CADD | 3.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.6%
African / African-American · 3,451/74,974 alleles
Filtering AF
4.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.42%
Overall
0.245%
3,950/1,613,578 alleles · low-frequency
exomes 1,961/1,461,346 · genomes 1,989/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.6% | 22 |
| Middle Eastern | 0.407% | 246 |
| Admixed American | 0.313% | 319 |
| Remaining individualsnot grpmax-eligible | 0.299% | 334 |
| South Asian | 0.00988% | 10,119 |
| European (non-Finnish) | 0.0078% | 12,826 |
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.Arg407=
- Coding
- c.1219C>A
- MANE Select
- NM_000526
- dbSNP
- rs149217449
- Type
- single nucleotide variant
- Location
- chr17:41583290 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.00 · 6 PDB
- Residue 407
- the if rod domain; the 'coil 2' region; an α-helix
Similar variants
- KRT14 p.Arg407Trp Uncertain significance ★★ ⚠ same residue
- KRT14 p.Arg407Gln Uncertain significance ★ same residue
- KRT14 p.Arg407Pro Uncertain significance ★ ⚠ 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
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-arg407 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown