KRT74 p.Ser356=
c.1068C>T · VCV4917004
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -20 | |
| Overall | ||
| CADD | 0.097 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,082 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00118%
19/1,613,986 alleles · ultra-rare
exomes 18/1,461,850 · genomes 1/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,041 |
| South Asian | 0.00549% | 18,216 |
| African / African-American | 0.00134% | 74,902 |
| European (non-Finnish) | 0.000932% | 107,273 |
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.Ser356=
- Coding
- c.1068C>T
- MANE Select
- NM_175053
- Type
- single nucleotide variant
- Location
- chr12:52569925 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 356
- the if rod domain; the 'coil 2' region
Similar variants
- 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
- KRT74 p.Leu364His 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-ser356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown