Is FSHR p.Gln117Ter (c.349C>T) pathogenic?

FSHR p.Gln117Ter (c.349C>T) is classified Pathogenic in FSHR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-01). Absent from gnomAD v4.1; Associated with Genetic non-acquired premature ovarian failure.

What condition is associated with FSHR p.Gln117Ter (c.349C>T)?

FSHR p.Gln117Ter (c.349C>T) is associated with Genetic non-acquired premature ovarian failure (ClinVar).

How common is FSHR p.Gln117Ter (c.349C>T) in the general population?

FSHR p.Gln117Ter (c.349C>T) is absent from gnomAD v4.1 (gnomAD).

FSHR p.Gln117Ter

c.349C>T · rs2104211236 · VCV1256023

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Genetic non-acquired premature ovarian failure

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	Δ0.24	acceptor loss, 46 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.3	GERP 2.6, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FSHR
Protein: p.Gln117Ter
Coding: c.349C>T
MANE Select: NM_000145
dbSNP: rs2104211236
Type: single nucleotide variant
Location: chr2:49017514 (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

Genetic non-acquired premature ovarian failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FSHR p.Gln117= Uncertain significance ★ same residue
FSHR p.Glu466Lys Likely pathogenic same condition
FSHR p.Ile588Thr Likely pathogenic same condition
FSHR p.Leu125Arg Likely pathogenic same condition
FSHR p.Ser295Phe Likely pathogenic ⚠ same condition
FSHR p.Thr228Ile Likely pathogenic same condition
FSHR p.Asn560fs Pathogenic same condition
FSHR p.Arg229Gly 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-gln117ter (accessed [today's date]).

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