Is GP9 p.Pro47Ser (c.139C>T) pathogenic?

GP9 p.Pro47Ser (c.139C>T) is classified Conflicting classifications of pathogenicity in GP9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-01). AlphaMissense: likely pathogenic (0.6504); Very rare (popmax 0.000678%, nfe); Associated with GP9-related disorders.

What condition is associated with GP9 p.Pro47Ser (c.139C>T)?

GP9 p.Pro47Ser (c.139C>T) is associated with GP9-related disorders (ClinVar).

How common is GP9 p.Pro47Ser (c.139C>T) in the general population?

GP9 p.Pro47Ser (c.139C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about GP9 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely pathogenic (score 0.6504) — an in-silico prediction, not a clinical call.

GP9 p.Pro47Ser

c.139C>T · VCV3768159

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GP9-related disorders

Computational evidence

Protein change
AlphaMissense	0.6504	likely pathogenic
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -11.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 530 bp · p 0.38 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,758 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,038 alleles · very rare exomes 7/1,460,802 · genomes 1/152,236 · joint denominator

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: GP9
Protein: p.Pro47Ser
Coding: c.139C>T
MANE Select: NM_000174
Type: single nucleotide variant
Location: chr3:129061878 (GRCh38)
Structure: AlphaFold pLDDT 84.43 · 2 PDB
Residue 47: an α-helix; the lrrnt domain

Full GP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GP9-related disorders

Similar variants

GP9 p.Val152Met Uncertain significance ★★ ⚠ same condition
GP9 p.Pro50Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
GP9 p.Arg145His Likely benign same condition
GP9 p.Cys113fs Likely pathogenic ★★ same condition
GP9 p.Asn61Ser Pathogenic ★★★ same type
GP9 p.Cys135Tyr Likely pathogenic ★★★ ⚠ same type
GP9 p.Cys24Arg Likely pathogenic ★★★ same type
GP9 p.Cys38Arg Likely pathogenic ★★★ same type

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/gp9-p-pro47ser (accessed [today's date]).

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