FGFR1 c.1663+9C>T
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, amr)
Conditions
2
Pfeiffer syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +9 | near-intronic (+9 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -4 |
| Non-coding constraint | Z 3.19 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 0.173 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
Admixed American · 15/60,018 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.00249%
40/1,605,500 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.025% | 4,001 |
| East Asian | 0.00892% | 11,207 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,754 |
| South Asian | 0.0022% | 45,462 |
| European (non-Finnish) | 0.00136% | 73,371 |
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
- Coding
- c.1663+9C>T
- MANE Select
- NM_023110
- dbSNP
- rs557754125
- Type
- single nucleotide variant
- Location
- chr8:38417297 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.30 · 86 PDB
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-c-1663-plus-9c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown