KDF1 p.Pro67=
c.201G>A · rs17162368 · VCV777325
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 9.7%, afr) — too common for a highly-penetrant pathogenic allele
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 -9.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.073 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.7%
African / African-American · 7,276/75,016 alleles
Filtering AF
9.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.44%
Overall
0.563%
9,085/1,613,304 alleles · common
exomes 4,858/1,461,036 · genomes 4,227/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.7% | 10 |
| Admixed American | 0.855% | 117 |
| Remaining individualsnot grpmax-eligible | 0.743% | 135 |
| Middle Eastern | 0.71% | 141 |
| European (non-Finnish) | 0.0633% | 1,579 |
| South Asian | 0.045% | 2,220 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,576 |
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
- KDF1
- Protein
- p.Pro67=
- Coding
- c.201G>A
- MANE Select
- NM_152365
- dbSNP
- rs17162368
- Type
- single nucleotide variant
- Location
- chr1:26952180 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 59.59
Similar variants
- KDF1 p.Pro67Leu Benign ★ same residue
- KDF1 p.Arg319Cys Uncertain significance ★★ ⚠ same type
- KDF1 p.Arg3His Uncertain significance ★★ ⚠ same type
- KDF1 p.Arg87Gln Uncertain significance ★★ ⚠ same type
- KDF1 p.Glu190Lys Uncertain significance ★★ ⚠ same type
- KDF1 p.Ser380Pro Uncertain significance ★★ ⚠ same type
- KDF1 p.Ser388Leu Uncertain significance ★★ ⚠ same type
- KDF1 c.1040-6C>T Benign/Likely benign ★★ 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/kdf1-p-pro67 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown