KRT74 p.Ala440=
c.1320C>T · VCV4797073
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.499%, eas)
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 2.8 | phastCons 1 |
| Overall | ||
| CADD | 11.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.499%
East Asian · 224/44,876 alleles
Filtering AF
0.446%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.425%
Overall
0.0149%
240/1,614,160 alleles · rare
exomes 206/1,461,886 · genomes 34/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.499% | 200 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| South Asian | 0.00878% | 11,386 |
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.Ala440=
- Coding
- c.1320C>T
- MANE Select
- NM_175053
- Type
- single nucleotide variant
- Location
- chr12:52568204 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 440
- 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-ala440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown