Is FSHR p.Leu601Val (c.1801C>G) pathogenic?

FSHR p.Leu601Val (c.1801C>G) is classified Likely pathogenic in FSHR (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1715); Absent from gnomAD v4.1; Associated with ovarian dysgenesis 1.

What condition is associated with FSHR p.Leu601Val (c.1801C>G)?

FSHR p.Leu601Val (c.1801C>G) is associated with ovarian dysgenesis 1 (ClinVar).

How common is FSHR p.Leu601Val (c.1801C>G) in the general population?

FSHR p.Leu601Val (c.1801C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FSHR p.Leu601Val (c.1801C>G)?

AlphaMissense predicts likely benign (score 0.1715) — an in-silico prediction, not a clinical call.

FSHR p.Leu601Val

c.1801C>G · rs386833513 · VCV56032

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1715 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian dysgenesis 1

Computational evidence

Protein change
AlphaMissense	0.1715	likely benign ⚠ discordant with ClinVar
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -10.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.3, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	27.2	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.Leu601Val
Coding: c.1801C>G
MANE Select: NM_000145
dbSNP: rs386833513
Type: single nucleotide variant
Location: chr2:48963020 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 601: a UniProt-annotated variant site (in odg1; binds fsh with a similar affinity than the wild-type receptor; adenylate cyclase stimulation by fsh is 12 +-3% residual activity)

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

Disease context

ovarian dysgenesis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FSHR p.Arg229Gly Uncertain significance ★★ ⚠ same condition
FSHR p.Arg557Trp Uncertain significance ★★ ⚠ same condition
FSHR p.Glu300Lys Uncertain significance ★★ ⚠ same condition
FSHR p.Glu319Gly Uncertain significance ★★ ⚠ same condition
FSHR p.Ile230Val Uncertain significance ★★ ⚠ same condition
FSHR p.Ile382Thr Uncertain significance ★★ ⚠ same condition
FSHR p.Lys133= Uncertain significance ★★ same condition
FSHR p.Met532Ile 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-leu601val (accessed [today's date]).

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