KRT74 p.Asp388=
c.1164C>T · rs185121430 · VCV2083259
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
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 | 0.752 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/60,020 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.0031%
50/1,614,232 alleles · ultra-rare
exomes 46/1,461,878 · genomes 4/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,159 |
| South Asian | 0.0121% | 8,281 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| African / African-American | 0.00133% | 75,066 |
| European (non-Finnish) | 0.00127% | 78,670 |
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.Asp388=
- Coding
- c.1164C>T
- MANE Select
- NM_175053
- dbSNP
- rs185121430
- Type
- single nucleotide variant
- Location
- chr12:52568360 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 388
- 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-asp388 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown