Is FSHR p.Phe69Cys (c.206T>G) pathogenic?

FSHR p.Phe69Cys (c.206T>G) is classified Uncertain significance in FSHR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.3656); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FSHR p.Phe69Cys (c.206T>G)?

FSHR p.Phe69Cys (c.206T>G) is associated with Inborn genetic diseases (ClinVar).

How common is FSHR p.Phe69Cys (c.206T>G) in the general population?

FSHR p.Phe69Cys (c.206T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FSHR p.Phe69Cys (c.206T>G)?

AlphaMissense predicts ambiguous (score 0.3656) — an in-silico prediction, not a clinical call.

FSHR p.Phe69Cys

c.206T>G · VCV4260255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3656 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3656	ambiguous
REVEL	0.705	pathogenic-leaning
SaProt	LLR -8.89	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	26.8	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: FSHR
Protein: p.Phe69Cys
Coding: c.206T>G
MANE Select: NM_000145
Type: single nucleotide variant
Location: chr2:49068237 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FSHR p.Arg557Trp Uncertain significance ★★ ⚠ same condition
FSHR p.Asp358Val Uncertain significance ★★ ⚠ same condition
FSHR p.Ile230Val Uncertain significance ★★ ⚠ same condition
FSHR p.Met532Ile Uncertain significance ★★ ⚠ same condition
FSHR p.Thr329Lys Uncertain significance ★★ ⚠ same condition
FSHR p.Ala352Val Uncertain significance ★ ⚠ same condition
FSHR p.Ala444Val Uncertain significance ★ ⚠ same condition
FSHR p.Ala474Val 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-phe69cys (accessed [today's date]).

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