Is FSHR p.Ser128Tyr (c.383C>A) pathogenic?

FSHR p.Ser128Tyr (c.383C>A) is classified Pathogenic in FSHR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-01-01). AlphaMissense: likely pathogenic (0.7328); Absent from gnomAD v4.1; Associated with ovarian hyperstimulation syndrome.

What condition is associated with FSHR p.Ser128Tyr (c.383C>A)?

FSHR p.Ser128Tyr (c.383C>A) is associated with ovarian hyperstimulation syndrome (ClinVar).

How common is FSHR p.Ser128Tyr (c.383C>A) in the general population?

FSHR p.Ser128Tyr (c.383C>A) is absent from gnomAD v4.1 (gnomAD).

How is Ovarian hyperstimulation syndrome inherited?

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

What do computational predictors say about FSHR p.Ser128Tyr (c.383C>A)?

AlphaMissense predicts likely pathogenic (score 0.7328) — an in-silico prediction, not a clinical call.

FSHR p.Ser128Tyr

c.383C>A · rs121909665 · VCV16254

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7328 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,492)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian hyperstimulation syndrome

Computational evidence

Protein change
AlphaMissense	0.7328	likely pathogenic ✓ concordant with ClinVar
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -9.67	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,604,492). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FSHR
Protein: p.Ser128Tyr
Coding: c.383C>A
MANE Select: NM_000145
dbSNP: rs121909665
Type: single nucleotide variant
Location: chr2:48990629 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 128: a UniProt-annotated variant site (in ohss; displays increase in affinity and sensitivity toward hcg and does not show any constitutive activity nor promiscuous activation by tsh); a β-strand

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

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-p-ser128tyr (accessed [today's date]).

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