Is GSN p.Val366= (c.1098G>A) pathogenic?

GSN p.Val366= (c.1098G>A) is classified Benign/Likely benign in GSN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0561%, nfe); Associated with Finnish type amyloidosis.

What condition is associated with GSN p.Val366= (c.1098G>A)?

GSN p.Val366= (c.1098G>A) is associated with Finnish type amyloidosis (ClinVar).

How common is GSN p.Val366= (c.1098G>A) in the general population?

GSN p.Val366= (c.1098G>A) is ultra-rare (popmax 0.0561%, nfe) (gnomAD).

How is AGel amyloidosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

GSN p.Val366=

c.1098G>A · rs201325199 · VCV364808

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, nfe)

Conditions

Finnish type amyloidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.8, phastCons 1
Overall
CADD	9.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% European (non-Finnish) · 662/1,180,008 alleles

Filtering AF 0.0525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0511%

Overall 0.0427% 690/1,614,160 alleles · ultra-rare exomes 653/1,461,830 · genomes 37/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0561%	1,782
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Finnishnot grpmax-eligible	0.0125%	8,001
Admixed American	0.005%	20,012
African / African-American	0.004%	25,015

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: GSN
Protein: p.Val366=
Coding: c.1098G>A
MANE Select: NM_198252
dbSNP: rs201325199
Type: single nucleotide variant
Location: chr9:121318787 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.76 · 65 PDB
Residue 366: an α-helix

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

Disease context

Finnish type amyloidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For AGel amyloidosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

GSN p.Val366Met Conflicting classifications of pathogenicity ★ ⚠ same residue
GSN p.Asn160Lys Pathogenic ★★ same condition
GSN p.Asp163Asn Pathogenic/Likely pathogenic ★★ same condition
GSN p.Asp163Tyr Pathogenic/Likely pathogenic ★★ same condition
GSN c.1762+2T>C Uncertain significance ★★ same condition
GSN c.513+1G>A Uncertain significance ★★ same condition
GSN c.753+1G>A Uncertain significance ★★ same condition
GSN c.754-1G>T 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/gsn-p-val366 (accessed [today's date]).

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