FSHR p.Ile561=
c.1683C>T · rs757713421 · VCV1675781
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 -1.9 | GERP -4.6 |
| Overall | ||
| CADD | 1.317 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,980 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000682%
11/1,613,984 alleles · very rare
exomes 10/1,461,830 · genomes 1/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,990 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000678% | 147,504 |
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
- FSHR
- Protein
- p.Ile561=
- Coding
- c.1683C>T
- MANE Select
- NM_000145
- dbSNP
- rs757713421
- Type
- single nucleotide variant
- Location
- chr2:48963138 (GRCh38)
- Gene constraint
- LOEUF 1.071 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.87 · 5 PDB
- Residue 561
- a turn
Similar variants
- FSHR p.Arg229Gly Uncertain significance ★★ ⚠ same type
- FSHR p.Arg557Trp Uncertain significance ★★ ⚠ same type
- FSHR p.Asp358Val Uncertain significance ★★ ⚠ same type
- FSHR p.Glu300Lys Uncertain significance ★★ ⚠ same type
- FSHR p.Glu319Gly Uncertain significance ★★ ⚠ same type
- FSHR p.Ile230Val Uncertain significance ★★ ⚠ same type
- FSHR p.Ile382Thr Uncertain significance ★★ ⚠ same type
- FSHR p.Lys133= 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/fshr-p-ile561 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown