KRT74 p.Ile372=
c.1116C>T · rs148938257 · VCV743365
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0946%, afr)
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 -4.3 | |
| Overall | ||
| CADD | 6.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0946%
African / African-American · 71/75,032 alleles
Filtering AF
0.0769%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0704%
Overall
0.0118%
190/1,614,126 alleles · ultra-rare
exomes 138/1,461,868 · genomes 52/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0946% | 1,057 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,945 |
| Admixed American | 0.01% | 10,004 |
| European (non-Finnish) | 0.0083% | 12,041 |
| Finnishnot grpmax-eligible | 0.00781% | 12,805 |
| South Asian | 0.0011% | 91,078 |
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.Ile372=
- Coding
- c.1116C>T
- MANE Select
- NM_175053
- dbSNP
- rs148938257
- Type
- single nucleotide variant
- Location
- chr12:52569877 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 372
- the if rod domain; the 'coil 2' region
Similar variants
- KRT74 p.Ile372Val 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-ile372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown