KERA p.Ser22=
c.66T>C · VCV3364635
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000255%, 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 0.35 | GERP -5, phastCons 0.2 |
| Overall | ||
| CADD | 5.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,177,212 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,609,674 alleles · very rare
exomes 3/1,458,416 · genomes 0/151,258 · joint denominator
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
- KERA
- Protein
- p.Ser22=
- Coding
- c.66T>C
- MANE Select
- NM_007035
- Type
- single nucleotide variant
- Location
- chr12:91056216 (GRCh38)
- Gene constraint
- LOEUF 1.284 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.42
Similar variants
- KERA p.Arg279Ter Pathogenic ★★ same type
- KERA p.Asn247Ser Pathogenic ★★ same type
- KERA p.Arg323Cys Uncertain significance ★★ ⚠ same type
- KERA p.Pro43His Uncertain significance ★★ ⚠ same type
- KERA c.887-8C>T Benign ★★ same type
- KERA p.Gln25= Benign ★★ same type
- KERA p.Val23= Benign ★★ same type
- KERA p.Arg313Ter 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/kera-p-ser22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown