Is GSN p.Phe101= (c.303C>T) pathogenic?

GSN p.Phe101= (c.303C>T) is classified Likely benign in GSN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-11). Ultra-rare (popmax 0.0213%, afr); Associated with Finnish type amyloidosis.

What condition is associated with GSN p.Phe101= (c.303C>T)?

GSN p.Phe101= (c.303C>T) is associated with Finnish type amyloidosis (ClinVar).

How common is GSN p.Phe101= (c.303C>T) in the general population?

GSN p.Phe101= (c.303C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

How is AGel amyloidosis inherited?

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

GSN p.Phe101=

c.303C>T · rs373779982 · VCV1623200

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, 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 -3.3	GERP -3.8
Overall
CADD	8.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/75,036 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00186% 30/1,613,968 alleles · ultra-rare exomes 16/1,461,674 · genomes 14/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,690
East Asian	0.00891%	11,222
South Asian	0.0011%	91,076
European (non-Finnish)	0.000763%	131,113

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.Phe101=
Coding: c.303C>T
MANE Select: NM_198252
dbSNP: rs373779982
Type: single nucleotide variant
Location: chr9:121303017 (GRCh38)
Gene constraint: LOEUF 0.788 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.76 · 65 PDB
Residue 101: a β-strand; 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.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-phe101 (accessed [today's date]).

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