KRT86 p.Ala334=
c.1002T>C · rs2032360 · VCV1252238
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 60.4%, afr) — too common for a highly-penetrant pathogenic allele
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 -3.8 |
| Overall | ||
| CADD | 0.972 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
60.4%
African / African-American · 44,363/73,482 alleles
Filtering AF
59.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 59.7%
Overall
35.1%
503,282/1,433,830 alleles · common
exomes 445,342/1,282,374 · genomes 57,940/151,456 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 60.4% | 2 |
| East Asian | 46.6% | 2 |
| Middle Eastern | 38.2% | 3 |
| Finnishnot grpmax-eligible | 36.8% | 3 |
| Remaining individualsnot grpmax-eligible | 35.6% | 3 |
| Admixed American | 33.8% | 3 |
| European (non-Finnish) | 33.4% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 33.3% | 3 |
| South Asian | 27.7% | 4 |
| Amishnot grpmax-eligible | 26.9% | 4 |
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
- KRT86
- Protein
- p.Ala334=
- Coding
- c.1002T>C
- MANE Select
- NM_001320198
- dbSNP
- rs2032360
- Type
- single nucleotide variant
- Location
- chr12:52305764 (GRCh38)
- Gene constraint
- LOEUF 1.044 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.50
- Residue 334
- the if rod domain; the 'coil 2' region
Similar variants
- KRT86 p.Ala293Asp Uncertain significance ★★ ⚠ same type
- KRT81 p.Ala359= Benign ★★ same type
- KRT86 c.1027-116G>A Benign ★★ same type
- KRT86 c.1027-15C>T Likely benign ★★ same type
- KRT86 c.1247+36C>A Benign ★★ same type
- KRT86 c.1248-152C>T Likely benign ★★ same type
- KRT86 c.370-9G>A Likely benign ★★ same type
- KRT86 c.578+178G>C 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/krt86-p-ala334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown