Is GSN p.Pro348Ser (c.1042C>T) pathogenic?

GSN p.Pro348Ser (c.1042C>T) is classified Uncertain significance in GSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.104); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GSN p.Pro348Ser (c.1042C>T)?

GSN p.Pro348Ser (c.1042C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GSN p.Pro348Ser (c.1042C>T) in the general population?

GSN p.Pro348Ser (c.1042C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GSN p.Pro348Ser (c.1042C>T)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

GSN p.Pro348Ser

c.1042C>T · VCV4835793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -2.17	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 4.9	GERP -0.49, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 31 kb · p 8.7e-05 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P399S vs ClinVar P348S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GSN
Protein: p.Pro348Ser
Coding: c.1042C>T
MANE Select: NM_198252
Type: single nucleotide variant
Location: chr9:121318731 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GSN p.Pro348= Likely benign ★★ same residue
GSN p.Pro348Leu Uncertain significance ★ ⚠ same residue
GSN c.753+1G>A Uncertain significance ★★ same condition
GSN c.-9-1983C>T Uncertain significance ★★ ⚠ same condition
GSN c.-9-1986C>T Uncertain significance ★★ ⚠ same condition
GSN c.-9-1987G>A Uncertain significance ★★ ⚠ same condition
GSN c.-9-2077G>A Uncertain significance ★★ ⚠ same condition
GSN c.-9-2088G>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-pro348ser (accessed [today's date]).

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