Is FSHR c.*246T>A pathogenic?

FSHR c.246T>A is classified Likely benign in FSHR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-03-29). Common (popmax 5.01%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ovarian hyperstimulation syndrome.

What condition is associated with FSHR c.*246T>A?

FSHR c.*246T>A is associated with ovarian hyperstimulation syndrome, ovarian dysgenesis 1 (ClinVar).

How is Ovarian hyperstimulation syndrome inherited?

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

FSHR c.*246T>A

Q: How common is FSHR c.*246T>A in the general population?

FSHR c.*246T>A is common (popmax 5.01%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs72825259 · VCV336476

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.01%, mid) — too common for a highly-penetrant pathogenic allele

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 1.2	GERP 1.2, phastCons 0.029
Non-coding constraint	Z -2.24	1 kb window · o/e 1.16 · regional · uncalibrated
Overall
CADD	2.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.01% Middle Eastern · 85/1,698 alleles

Filtering AF 4.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.83%

Overall 2.61% 12,697/487,370 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.01%	20
South Asian	3.46%	29
European (non-Finnish)	3.22%	31
Remaining individualsnot grpmax-eligible	2.56%	39
Finnishnot grpmax-eligible	2.45%	41
Ashkenazi Jewishnot grpmax-eligible	2.44%	41
Admixed American	1.67%	60
African / African-American	0.573%	175
Amishnot grpmax-eligible	0.11%	912
East Asian	0.0235%	4,263

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.*246T>A
MANE Select: NM_000145
dbSNP: rs72825259
Type: single nucleotide variant
Location: chr2:48962487 (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-246t-a (accessed [today's date]).

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