KRT74 p.Ser96=
c.288T>C · rs138196190 · VCV1224684
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 15.9%, amr) — 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 -2.3 | |
| Overall | ||
| CADD | 0.663 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15.9%
Admixed American · 9,557/60,030 alleles
Filtering AF
15.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 15.5%
Overall
0.719%
11,606/1,614,170 alleles · common
exomes 9,342/1,461,852 · genomes 2,264/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 15.9% | 6 |
| Finnishnot grpmax-eligible | 1.34% | 75 |
| Remaining individualsnot grpmax-eligible | 0.737% | 136 |
| African / African-American | 0.265% | 377 |
| European (non-Finnish) | 0.0441% | 2,269 |
| East Asian | 0.0111% | 8,977 |
| South Asian | 0.00549% | 18,216 |
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
- KRT74
- Protein
- p.Ser96=
- Coding
- c.288T>C
- MANE Select
- NM_175053
- dbSNP
- rs138196190
- Type
- single nucleotide variant
- Location
- chr12:52573490 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 96
- the 'head' region
Similar variants
- KRT74 p.Ser96Cys Uncertain significance ★ ⚠ same residue
- KRT74 p.Ala410Thr Uncertain significance ★★ ⚠ same type
- KRT74 p.Arg141Gln Uncertain significance ★★ ⚠ same type
- KRT74 p.Arg346Gln Uncertain significance ★★ ⚠ same type
- KRT74 p.Arg69Trp Uncertain significance ★★ ⚠ same type
- KRT74 p.Asp221Val Uncertain significance ★★ ⚠ same type
- KRT74 p.Gln426Arg Uncertain significance ★★ ⚠ same type
- KRT74 p.Ile7Ser Uncertain significance ★★ ⚠ 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/krt74-p-ser96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown