FSHR c.374+69T>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 80.1%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +69 | deep intronic (+69 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.64 | GERP -4.4, phastCons 0.001 |
| Non-coding constraint | Z -2.17 | 1 kb window · o/e 1.20 · regional · uncalibrated |
| Overall | ||
| CADD | 3.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
80.1%
East Asian · 33,553/41,870 alleles
Filtering AF
79.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 79.1%
Overall
51.3%
599,474/1,167,624 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 80.1% | 1 |
| Admixed American | 68.7% | 1 |
| South Asian | 54.7% | 2 |
| African / African-American | 54.1% | 2 |
| Remaining individualsnot grpmax-eligible | 52.2% | 2 |
| Middle Eastern | 50.8% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 48.9% | 2 |
| European (non-Finnish) | 48.4% | 2 |
| Finnishnot grpmax-eligible | 45.4% | 2 |
| Amishnot grpmax-eligible | 37.6% | 3 |
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
- Coding
- c.374+69T>C
- MANE Select
- NM_000145
- dbSNP
- rs2091787
- Type
- single nucleotide variant
- Location
- chr2:49017420 (GRCh38)
- Gene constraint
- LOEUF 1.071 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.87 · 5 PDB
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-c-374-plus-69t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown