FGFR1 p.Asp682=
c.2046T>C · rs749546240 · VCV2937509
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, sas)
Conditions
2
hypogonadotropic hypogonadism 2 with or without anosmia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -3.3 |
| Overall | ||
| CADD | 4.228 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
South Asian · 13/91,078 alleles
Filtering AF
0.00844%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.000958%
14/1,461,766 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0143% | 7,006 |
| European (non-Finnish) | 8.47e-05% | 1,179,984 |
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.Asp682=
- Coding
- c.2046T>C
- MANE Select
- NM_023110
- dbSNP
- rs749546240
- Type
- single nucleotide variant
- Location
- chr8:38414561 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.30 · 86 PDB
- Residue 682
- a UniProt-annotated variant site (in hh2); an α-helix; the protein kinase domain
Similar variants
- FGFR1 p.Asp682Asn Likely pathogenic ★ same residue
- 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
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-asp682 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown