Is GSN p.Pro29= (c.87C>T) pathogenic?

GSN p.Pro29= (c.87C>T) is classified Conflicting classifications of pathogenicity in GSN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-12). Very rare (popmax 0.0022%, sas); Associated with Finnish type amyloidosis.

What condition is associated with GSN p.Pro29= (c.87C>T)?

GSN p.Pro29= (c.87C>T) is associated with Finnish type amyloidosis (ClinVar).

How common is GSN p.Pro29= (c.87C>T) in the general population?

GSN p.Pro29= (c.87C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is AGel amyloidosis inherited?

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

GSN p.Pro29=

c.87C>T · rs757046360 · VCV1914064

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Finnish type amyloidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000743% 12/1,614,234 alleles · very rare exomes 12/1,461,886 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,544
Admixed American	0.00167%	60,032
African / African-American	0.00133%	75,062
European (non-Finnish)	0.000678%	147,505

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.Pro29=
Coding: c.87C>T
MANE Select: NM_198252
dbSNP: rs757046360
Type: single nucleotide variant
Location: chr9:121302058 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.76 · 65 PDB

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.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
GSN c.-9-1981C>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-pro29 (accessed [today's date]).

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