HGF p.Pro157=
c.471A>G · rs142045938 · VCV227427
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0336%, mid)
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 0.74 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 9.796 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0336%
Middle Eastern · 2/5,956 alleles
Filtering AF
0.016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0152%
Overall
0.0143%
221/1,542,856 alleles · ultra-rare
exomes 200/1,390,664 · genomes 21/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0336% | 2,978 |
| Remaining individualsnot grpmax-eligible | 0.0217% | 4,617 |
| European (non-Finnish) | 0.0181% | 5,520 |
| Admixed American | 0.00501% | 19,968 |
| African / African-American | 0.00136% | 73,652 |
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
- HGF
- Protein
- p.Pro157=
- Coding
- c.471A>G
- MANE Select
- NM_000601
- dbSNP
- rs142045938
- Type
- single nucleotide variant
- Location
- chr7:81757200 (GRCh38)
- Gene constraint
- LOEUF 0.471 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 36 PDB
- Residue 157
- the kringle 1 domain; a β-strand
Similar variants
- HGF p.Ala432Val Uncertain significance ★★ ⚠ same type
- HGF p.Ala661Thr Uncertain significance ★★ ⚠ same type
- HGF p.Arg168Trp Uncertain significance ★★ ⚠ same type
- HGF p.Arg220Gln Uncertain significance ★★ ⚠ same type
- HGF p.Arg242Gln Uncertain significance ★★ ⚠ same type
- HGF p.Arg242Trp Uncertain significance ★★ ⚠ same type
- HGF p.Arg328His Uncertain significance ★★ ⚠ same type
- HGF p.Arg350Gln 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/hgf-p-pro157 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown