KRT4 p.Ser486=
c.1458T>C · VCV4917049
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0758%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.35 | GERP -3, phastCons 0.019 |
| Overall | ||
| CADD | 5.958 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0758%
East Asian · 34/44,874 alleles
Filtering AF
0.0557%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0488%
Overall
0.00595%
96/1,614,104 alleles · ultra-rare
exomes 78/1,461,862 · genomes 18/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0758% | 1,320 |
| Admixed American | 0.04% | 2,501 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0154% | 6,506 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| African / African-American | 0.004% | 25,008 |
| European (non-Finnish) | 0.00102% | 98,332 |
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
- KRT4
- Protein
- p.Ser486=
- Coding
- c.1458T>C
- MANE Select
- NM_002272
- Type
- single nucleotide variant
- Location
- chr12:52807174 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.77
- Residue 486
- the 'tail' region
Similar variants
- KRT4 p.Ser486Gly Likely benign ★ same residue
- KRT4 p.Ala106Gly Uncertain significance ★★ ⚠ same type
- KRT4 p.Asp153Asn Uncertain significance ★★ ⚠ same type
- KRT4 p.Asp247Glu Uncertain significance ★★ same type
- KRT4 c.1126-32G>A Benign ★★ same type
- KRT4 c.1346+15A>G Benign ★★ same type
- KRT4 c.1346+15A>T Likely benign ★★ same type
- KRT4 c.1381+15C>T 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/krt4-p-ser486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown