Is FSHR p.Thr329= (c.987G>T) pathogenic?

FSHR p.Thr329= (c.987G>T) is classified Likely benign in FSHR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-15). Ultra-rare (popmax 0.0164%, mid); Associated with FSHR-related disorder.

What condition is associated with FSHR p.Thr329= (c.987G>T)?

FSHR p.Thr329= (c.987G>T) is associated with FSHR-related disorder (ClinVar).

How common is FSHR p.Thr329= (c.987G>T) in the general population?

FSHR p.Thr329= (c.987G>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

FSHR p.Thr329=

c.987G>T · rs6168 · VCV3041769

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

FSHR-related disorder

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 0.32	GERP -2.7, phastCons 0.019
Overall
CADD	0.929	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,613,990 alleles · ultra-rare exomes 7/1,461,862 · genomes 1/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000508%	196,668

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.Thr329=
Coding: c.987G>T
MANE Select: NM_000145
dbSNP: rs6168
Type: single nucleotide variant
Location: chr2:48963834 (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

FSHR-related disorder

Similar variants

FSHR p.Thr329Lys Uncertain significance ★★ ⚠ same residue
FSHR p.Ala189Val Pathogenic ★ ⚠ same condition
FSHR p.Ile160Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
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

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-thr329 (accessed [today's date]).

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