Is FSHR c.*321A>T pathogenic?

FSHR c.321A>T is classified Conflicting classifications of pathogenicity in FSHR (ClinVar, Conflicting submitters, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.433%, eas); Associated with ovarian hyperstimulation syndrome.

What condition is associated with FSHR c.*321A>T?

FSHR c.*321A>T is associated with ovarian hyperstimulation syndrome, ovarian dysgenesis 1 (ClinVar).

How common is FSHR c.*321A>T in the general population?

FSHR c.*321A>T is rare (popmax 0.433%, eas) (gnomAD).

How is Ovarian hyperstimulation syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

FSHR c.*321A>T

rs117897604 · VCV897606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.433%, eas)

Conditions

ovarian hyperstimulation syndrome

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	GERP -3.9
Non-coding constraint	Z -2.24	1 kb window · o/e 1.16 · regional · uncalibrated
Overall
CADD	0.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.433% East Asian · 56/12,932 alleles

Filtering AF 0.342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.31%

Overall 0.0174% 58/333,498 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.433%	231
Remaining individualsnot grpmax-eligible	0.0176%	5,695

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.*321A>T
MANE Select: NM_000145
dbSNP: rs117897604
Type: single nucleotide variant
Location: chr2:48962412 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB

Full FSHR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian hyperstimulation syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian dysgenesis 1

For Ovarian hyperstimulation syndrome (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult

Similar variants

FSHR p.Arg229Gly Uncertain significance ★★ ⚠ same condition
FSHR p.Arg557Trp Uncertain significance ★★ ⚠ same condition
FSHR p.Glu300Lys Uncertain significance ★★ ⚠ same condition
FSHR p.Glu319Gly Uncertain significance ★★ ⚠ same condition
FSHR p.Ile230Val Uncertain significance ★★ ⚠ same condition
FSHR p.Ile382Thr Uncertain significance ★★ ⚠ same condition
FSHR p.Lys133= Uncertain significance ★★ same condition
FSHR p.Met532Ile Uncertain significance ★★ ⚠ 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/fshr-c-star-321a-t (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown