KDF1 p.Pro18=
c.54G>A · rs139077715 · VCV2174963
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.119%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.39 | GERP -3.8, phastCons 0.98 |
| Overall | ||
| CADD | 11.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.119%
African / African-American · 86/72,304 alleles
Filtering AF
0.0987%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0911%
Overall
0.00801%
122/1,524,000 alleles · rare
exomes 50/1,371,718 · genomes 72/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.119% | 841 |
| Admixed American | 0.0273% | 3,658 |
| Remaining individualsnot grpmax-eligible | 0.0137% | 7,316 |
| Finnishnot grpmax-eligible | 0.00343% | 29,161 |
| South Asian | 0.0013% | 76,964 |
| European (non-Finnish) | 0.00106% | 94,659 |
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.Pro18=
- Coding
- c.54G>A
- MANE Select
- NM_152365
- dbSNP
- rs139077715
- Type
- single nucleotide variant
- Location
- chr1:26952327 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 59.59
- Residue 18
- the 'disordered' region
Similar variants
- 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
- KDF1 p.Arg101His 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-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown