Is FSHR p.Cys672Tyr (c.2015G>A) pathogenic?

FSHR p.Cys672Tyr (c.2015G>A) is classified Uncertain significance in FSHR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely benign (0.0625); Very rare (popmax 0.00333%, amr).

How common is FSHR p.Cys672Tyr (c.2015G>A) in the general population?

FSHR p.Cys672Tyr (c.2015G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about FSHR p.Cys672Tyr (c.2015G>A)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

FSHR p.Cys672Tyr

c.2015G>A · VCV4075609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	12.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00131% 2/152,184 alleles · very rare

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.Cys672Tyr
Coding: c.2015G>A
MANE Select: NM_000145
Type: single nucleotide variant
Location: chr2:48962806 (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

Similar variants

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
FSHR p.Ile230Val Uncertain significance ★★ ⚠ same type
FSHR p.Ile382Thr Uncertain significance ★★ ⚠ same type
FSHR p.Lys133= 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-cys672tyr (accessed [today's date]).

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