KRT74 p.Ala419=
c.1257G>A · rs143744119 · VCV781072
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.24%, 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 -3.5 | |
| Overall | ||
| CADD | 6.669 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.24%
African / African-American · 1,679/75,028 alleles
Filtering AF
2.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.11%
Overall
0.122%
1,972/1,614,170 alleles · low-frequency
exomes 936/1,461,878 · genomes 1,036/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.24% | 45 |
| Admixed American | 0.158% | 632 |
| Remaining individualsnot grpmax-eligible | 0.15% | 665 |
| Middle Eastern | 0.115% | 866 |
| East Asian | 0.0245% | 4,080 |
| European (non-Finnish) | 0.00686% | 14,568 |
| South Asian | 0.00439% | 22,773 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
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.Ala419=
- Coding
- c.1257G>A
- MANE Select
- NM_175053
- dbSNP
- rs143744119
- Type
- single nucleotide variant
- Location
- chr12:52568267 (GRCh38)
- Gene constraint
- LOEUF 1.278 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.11
- Residue 419
- 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-ala419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown