Is FSHR p.Arg162Lys (c.485G>A) pathogenic?

FSHR p.Arg162Lys (c.485G>A) is classified Conflicting classifications of pathogenicity in FSHR (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-11-15). AlphaMissense: likely benign (0.0674); Rare (popmax 0.491%, nfe); Associated with ovarian dysgenesis 1.

What condition is associated with FSHR p.Arg162Lys (c.485G>A)?

FSHR p.Arg162Lys (c.485G>A) is associated with ovarian dysgenesis 1, ovarian hyperstimulation syndrome (ClinVar).

How common is FSHR p.Arg162Lys (c.485G>A) in the general population?

FSHR p.Arg162Lys (c.485G>A) is rare (popmax 0.491%, nfe) (gnomAD).

What do computational predictors say about FSHR p.Arg162Lys (c.485G>A)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

FSHR p.Arg162Lys

c.485G>A · rs111883853 · VCV336489

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.491%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian dysgenesis 1

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 0.91, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	16.32	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

Grpmax group 0.491% European (non-Finnish) · 5,788/1,179,826 alleles

Filtering AF 0.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.476%

Overall 0.423% 6,833/1,613,862 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.12%	90
European (non-Finnish)grpmax	0.491%	204
Remaining individualsnot grpmax-eligible	0.328%	305
Admixed American	0.0816%	1,225
African / African-American	0.076%	1,316
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
Middle Eastern	0.033%	3,031
South Asian	0.0022%	45,540

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg162Lys
Coding: c.485G>A
MANE Select: NM_000145
dbSNP: rs111883853
Type: single nucleotide variant
Location: chr2:48989016 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 162: a turn

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

Also linked: ovarian hyperstimulation syndrome

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-arg162lys (accessed [today's date]).

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