Is FSHR p.Arg573Cys (c.1717C>T) pathogenic?

FSHR p.Arg573Cys (c.1717C>T) is classified Pathogenic in FSHR (ClinVar, No assertion criteria, 1 submitter; last evaluated 1998-10-01). AlphaMissense: likely benign (0.2716); Very rare (popmax 0.0011%, nfe); Associated with ovarian dysgenesis 1.

What condition is associated with FSHR p.Arg573Cys (c.1717C>T)?

FSHR p.Arg573Cys (c.1717C>T) is associated with ovarian dysgenesis 1 (ClinVar).

How common is FSHR p.Arg573Cys (c.1717C>T) in the general population?

FSHR p.Arg573Cys (c.1717C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about FSHR p.Arg573Cys (c.1717C>T)?

AlphaMissense predicts likely benign (score 0.2716) — an in-silico prediction, not a clinical call.

FSHR p.Arg573Cys

c.1717C>T · rs121909660 · VCV16245

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian dysgenesis 1

Computational evidence

Protein change
AlphaMissense	0.2716	likely benign ⚠ discordant with ClinVar
REVEL	0.763	pathogenic-leaning
SaProt	LLR -12.37	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	33.0	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 0.0011% European (non-Finnish) · 13/1,179,986 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,066 alleles · very rare exomes 14/1,461,814 · genomes 0/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0011%	90,768
South Asian	0.0011%	91,068

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.Arg573Cys
Coding: c.1717C>T
MANE Select: NM_000145
dbSNP: rs121909660
Type: single nucleotide variant
Location: chr2:48963104 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 573: an α-helix; a UniProt-annotated variant site (in odg1; alters signal transduction of the receptor; adenylate cyclase stimulation by fsh is 24 +-4% residual activity)

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

Disease context

ovarian dysgenesis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg573cys (accessed [today's date]).

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