Is GSN p.Ala92= (c.276C>T) pathogenic?

GSN p.Ala92= (c.276C>T) is classified Likely benign in GSN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.028%, afr); Associated with Finnish type amyloidosis.

What condition is associated with GSN p.Ala92= (c.276C>T)?

GSN p.Ala92= (c.276C>T) is associated with Finnish type amyloidosis (ClinVar).

How common is GSN p.Ala92= (c.276C>T) in the general population?

GSN p.Ala92= (c.276C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

How is AGel amyloidosis inherited?

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

GSN p.Ala92=

c.276C>T · rs548138013 · VCV738729

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

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 -9.8	GERP -3.5
Overall
CADD	0.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/75,052 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00384% 62/1,613,990 alleles · ultra-rare exomes 48/1,461,654 · genomes 14/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,574
Middle Eastern	0.0165%	6,062
East Asian	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.00254%	39,334
Admixed American	0.00167%	60,030
South Asian	0.0011%	91,086

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.Ala92=
Coding: c.276C>T
MANE Select: NM_198252
dbSNP: rs548138013
Type: single nucleotide variant
Location: chr9:121302990 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.76 · 65 PDB
Residue 92: a binding site; the 'actin-severing' region

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.Ala92Ser Uncertain significance ★ ⚠ 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-ala92 (accessed [today's date]).

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