HGFAC p.Ser568=
c.1704C>T · VCV3857706
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.152%, nfe)
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 1.2 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 7.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.152%
European (non-Finnish) · 1,795/1,177,666 alleles
Filtering AF
0.147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.144%
Overall
0.118%
1,901/1,605,960 alleles · rare
exomes 1,827/1,453,758 · genomes 74/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.152% | 656 |
| Remaining individualsnot grpmax-eligible | 0.127% | 786 |
| Middle Eastern | 0.0203% | 4,934 |
| African / African-American | 0.0147% | 6,802 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0136% | 7,352 |
| Finnishnot grpmax-eligible | 0.0129% | 7,751 |
| Admixed American | 0.00336% | 29,735 |
| South Asian | 0.00111% | 89,906 |
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
- HGFAC
- Protein
- p.Ser568=
- Coding
- c.1704C>T
- MANE Select
- NM_001528
- Type
- single nucleotide variant
- Location
- chr4:3448195 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 7 PDB
- Residue 568
- the peptidase s1 domain
Similar variants
- HGFAC p.Ala121Pro Uncertain significance ★ ⚠ same type
- HGFAC p.Ala268Ser Uncertain significance ★ ⚠ same type
- HGFAC p.Ala274Thr Uncertain significance ★ ⚠ same type
- HGFAC p.Ala327Val Uncertain significance ★ ⚠ same type
- HGFAC p.Ala328Val Uncertain significance ★ ⚠ same type
- HGFAC p.Ala356Val Uncertain significance ★ ⚠ same type
- HGFAC p.Ala424Pro Uncertain significance ★ ⚠ same type
- HGFAC p.Ala446Ser 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/hgfac-p-ser568 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown