Is TSHR p.Phe97Val (c.289T>G) pathogenic?

TSHR p.Phe97Val (c.289T>G) is classified Likely pathogenic in TSHR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely pathogenic (0.8021); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with TSHR p.Phe97Val (c.289T>G)?

TSHR p.Phe97Val (c.289T>G) is associated with ovarian cancer (ClinVar).

How common is TSHR p.Phe97Val (c.289T>G) in the general population?

TSHR p.Phe97Val (c.289T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TSHR p.Phe97Val (c.289T>G)?

AlphaMissense predicts likely pathogenic (score 0.8021) — an in-silico prediction, not a clinical call.

TSHR p.Phe97Val

c.289T>G · rs2503498523 · VCV2445353

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8021 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.8021	likely pathogenic ✓ concordant with ClinVar
REVEL	0.73	pathogenic-leaning
SaProt	LLR -11.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 189 kb · p 0.032 · regional, not allelic
Overall
CADD	26.7	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

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: TSHR
Protein: p.Phe97Val
Coding: c.289T>G
MANE Select: NM_000369
dbSNP: rs2503498523
Type: single nucleotide variant
Location: chr14:81068300 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 9 PDB
Residue 97: a β-strand

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

Disease context

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

Similar variants

TSHR p.Phe97Ser Uncertain significance ★ ⚠ same residue
TSHR p.Arg450His Pathogenic/Likely pathogenic ★★ ⚠ same condition
TSHR p.Gly132Arg Likely pathogenic ★★ same condition
TSHR p.Met164Lys Likely pathogenic ★ same condition
TSHR p.Thr165Met Likely pathogenic ★ ⚠ same condition
TSHR p.Thr607Arg Likely pathogenic ★ ⚠ same condition
TSHR p.Lys700Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
TSHR p.Phe525Ser Conflicting classifications of pathogenicity ★ ⚠ 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/tshr-p-phe97val (accessed [today's date]).

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