FGF12 p.Ser76=
c.228A>G · rs200576975 · VCV1012711
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 0.96 | GERP -0.76, phastCons 1 |
| Overall | ||
| CADD | 8.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,056 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.00444%
71/1,600,096 alleles · ultra-rare
exomes 65/1,448,090 · genomes 6/152,006 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,019 |
| European (non-Finnish) | 0.00565% | 17,692 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 31,000 |
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
- FGF12
- Protein
- p.Ser76=
- Coding
- c.228A>G
- MANE Select
- NM_004113
- dbSNP
- rs200576975
- Type
- single nucleotide variant
- Location
- chr3:192335361 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.91 · 2 PDB
- Residue 76
- a β-strand
Similar variants
- FGF12 p.Arg52His Pathogenic/Likely pathogenic ★★ same type
- FGF12 p.Gly50Ser Pathogenic/Likely pathogenic ★★ same type
- FGF12 c.125-3C>G Uncertain significance ★★ same type
- FGF12 c.14-47513G>T Uncertain significance ★★ ⚠ same type
- FGF12 c.14-47520A>G Uncertain significance ★★ ⚠ same type
- FGF12 c.14-47558G>C Uncertain significance ★★ ⚠ same type
- FGF12 c.14-47562G>A Uncertain significance ★★ same type
- FGF12 c.14-47655C>T 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/fgf12-p-ser76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown