KRT85 p.Val438Ala
c.1313T>C · rs145033594 · VCV2078791
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1287 | likely benign |
|---|---|---|
| REVEL | 0.343 | indeterminate |
| SaProt | LLR -7.28 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.39 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 6,136 bp · p 0.65 · regional, not allelic |
| Overall | ||
| CADD | 23.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0375% | 2,668 |
| European (non-Finnish)grpmax | 0.0365% | 2,738 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,905 |
| African / African-American | 0.0147% | 6,811 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,802 |
| Admixed American | 0.00333% | 30,005 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- KRT85
- Protein
- p.Val438Ala
- Coding
- c.1313T>C
- MANE Select
- NM_002283
- dbSNP
- rs145033594
- Type
- single nucleotide variant
- Location
- chr12:52361484 (GRCh38)
- Gene constraint
- LOEUF 0.89 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09
- Residue 438
- the 'tail' region
Similar variants
- KRT85 p.Arg142His Uncertain significance ★★ ⚠ same type
- KRT85 p.Arg315His Uncertain significance ★★ ⚠ same type
- KRT85 p.Arg465His Uncertain significance ★★ ⚠ same type
- KRT85 p.Asn115Lys Uncertain significance ★★ ⚠ same type
- KRT85 p.Glu352Lys Uncertain significance ★★ ⚠ same type
- KRT85 p.Gly390Ser Uncertain significance ★★ ⚠ same type
- KRT85 p.Gly89Arg Uncertain significance ★★ ⚠ same type
- KRT85 c.1078-17G>A Benign/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/krt85-p-val438ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown