Is FSHR p.Cys584= (c.1752C>T) pathogenic?

FSHR p.Cys584= (c.1752C>T) is classified Uncertain significance in FSHR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-26). Ultra-rare (popmax 0.045%, amr).

How common is FSHR p.Cys584= (c.1752C>T) in the general population?

FSHR p.Cys584= (c.1752C>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

FSHR p.Cys584=

c.1752C>T · rs768038206 · VCV3047465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

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 4.6	GERP 2.3, phastCons 1
Overall
CADD	7.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/59,976 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00173% 28/1,613,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,221
European (non-Finnish)	8.47e-05%	1,180,002

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.Cys584=
Coding: c.1752C>T
MANE Select: NM_000145
dbSNP: rs768038206
Type: single nucleotide variant
Location: chr2:48963069 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 584: an α-helix

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

Similar variants

FSHR p.Arg229Gly Uncertain significance ★★ ⚠ same type
FSHR p.Arg557Trp Uncertain significance ★★ ⚠ same type
FSHR p.Asp358Val Uncertain significance ★★ ⚠ same type
FSHR p.Glu300Lys Uncertain significance ★★ ⚠ same type
FSHR p.Glu319Gly Uncertain significance ★★ ⚠ same type
FSHR p.Ile230Val Uncertain significance ★★ ⚠ same type
FSHR p.Ile382Thr Uncertain significance ★★ ⚠ same type
FSHR p.Lys133= Uncertain significance ★★ same type

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-cys584 (accessed [today's date]).

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