FGFR1 p.Val511=
c.1533G>C · VCV4788266
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
Conditions
2
hypogonadotropic hypogonadism 2 with or without anosmia
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 1.5 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 10.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,908 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000496%
8/1,614,068 alleles · ultra-rare
exomes 6/1,461,890 · genomes 2/152,178 · joint denominator
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
- FGFR1
- Protein
- p.Val511=
- Coding
- c.1533G>C
- MANE Select
- NM_023110
- Type
- single nucleotide variant
- Location
- chr8:38417889 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.30 · 86 PDB
- Residue 511
- a β-strand; the protein kinase domain; a UniProt-annotated variant site (in hh2)
Similar variants
- FGFR1 c.1977+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FGFR1 c.1977+1G>T Pathogenic/Likely pathogenic ★★ same condition
- FGFR1 c.448+1G>A Likely pathogenic ★★ same condition
- FGFR1 c.449-6G>A Likely pathogenic ★★ same condition
- FGFR1 c.91+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FGFR1 p.Arg209Cys Likely pathogenic ★★ same condition
- FGFR1 p.Arg250Gln Pathogenic ★★ same condition
- FGFR1 p.Arg250Trp Pathogenic/Likely pathogenic ★★ same condition
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/fgfr1-p-val511 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown