Is FSHR p.Val341Ala (c.1022T>C) pathogenic?

FSHR p.Val341Ala (c.1022T>C) is classified Conflicting classifications of pathogenicity in FSHR (ClinVar, Conflicting submitters, 1 submitter; last evaluated 2017-04-27). AlphaMissense: likely benign (0.0791); Rare (popmax 0.115%, nfe); Associated with ovarian hyperstimulation syndrome.

What condition is associated with FSHR p.Val341Ala (c.1022T>C)?

FSHR p.Val341Ala (c.1022T>C) is associated with ovarian hyperstimulation syndrome, ovarian dysgenesis 1 (ClinVar).

How common is FSHR p.Val341Ala (c.1022T>C) in the general population?

FSHR p.Val341Ala (c.1022T>C) is rare (popmax 0.115%, nfe) (gnomAD).

How is Ovarian hyperstimulation syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FSHR p.Val341Ala (c.1022T>C)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

FSHR p.Val341Ala

c.1022T>C · rs139226976 · VCV898832

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian hyperstimulation syndrome

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -7.22	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 1.3	GERP 1.2, phastCons 0.006
Regional constraint	o/e 1.16	unconstrained · MANE · 192 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	11.21	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 0.115% European (non-Finnish) · 1,353/1,179,990 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0898% 1,449/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.115%	872
Remaining individualsnot grpmax-eligible	0.0704%	1,421
Admixed American	0.0483%	2,069
African / African-American	0.0173%	5,772
Middle Eastern	0.0165%	6,060
Finnishnot grpmax-eligible	0.00937%	10,673
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
East Asian	0.00223%	44,874

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.Val341Ala
Coding: c.1022T>C
MANE Select: NM_000145
dbSNP: rs139226976
Type: single nucleotide variant
Location: chr2:48963799 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.87 · 5 PDB
Residue 341: a disulfide bond

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

Disease context

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

Also linked: ovarian dysgenesis 1

For Ovarian hyperstimulation syndrome (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult

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-val341ala (accessed [today's date]).

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