Is FSHR p.Gln152Pro (c.455A>C) pathogenic?

FSHR p.Gln152Pro (c.455A>C) is classified Uncertain significance in FSHR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). AlphaMissense: likely pathogenic (0.767); Very rare (popmax 0.00161%, nfe); Associated with ovarian hyperstimulation syndrome.

What condition is associated with FSHR p.Gln152Pro (c.455A>C)?

FSHR p.Gln152Pro (c.455A>C) is associated with ovarian hyperstimulation syndrome, ovarian dysgenesis 1 (ClinVar).

How common is FSHR p.Gln152Pro (c.455A>C) in the general population?

FSHR p.Gln152Pro (c.455A>C) is very rare (popmax 0.00161%, nfe) (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.Gln152Pro (c.455A>C)?

AlphaMissense predicts likely pathogenic (score 0.767) — an in-silico prediction, not a clinical call.

FSHR p.Gln152Pro

c.455A>C · rs377031489 · VCV895933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian hyperstimulation syndrome

Computational evidence

Protein change
AlphaMissense	0.767	likely pathogenic
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00161% European (non-Finnish) · 19/1,178,980 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000831%

Overall 0.00124% 20/1,612,724 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,052
African / African-American	0.00134%	74,904

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.Gln152Pro
Coding: c.455A>C
MANE Select: NM_000145
dbSNP: rs377031489
Type: single nucleotide variant
Location: chr2:48989046 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 152: 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

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-p-gln152pro (accessed [today's date]).

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