Is GP1BA p.Ser378Pro (c.1132T>C) pathogenic?

GP1BA p.Ser378Pro (c.1132T>C) is classified Uncertain significance in GP1BA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-16). AlphaMissense: likely benign (0.0663); Very rare (popmax 0.0028%, nfe); Associated with GP1BA-related disorder.

What condition is associated with GP1BA p.Ser378Pro (c.1132T>C)?

GP1BA p.Ser378Pro (c.1132T>C) is associated with GP1BA-related disorder (ClinVar).

How common is GP1BA p.Ser378Pro (c.1132T>C) in the general population?

GP1BA p.Ser378Pro (c.1132T>C) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about GP1BA p.Ser378Pro (c.1132T>C)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

GP1BA p.Ser378Pro

c.1132T>C · VCV3354069

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GP1BA-related disorder

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -4.73	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 -2.3	GERP -2.5
Regional constraint	o/e 0.89	unconstrained · MANE · 1,223 bp · p 0.011 · regional, not allelic
Overall
CADD	1.216	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% European (non-Finnish) · 33/1,179,748 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00205% 33/1,613,244 alleles · very rare exomes 32/1,461,706 · genomes 1/151,538 · 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: GP1BA
Protein: p.Ser378Pro
Coding: c.1132T>C
MANE Select: NM_000173
Type: single nucleotide variant
Location: chr17:4933736 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB
Residue 378: the 'disordered' region

Full GP1BA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GP1BA-related disorder

Similar variants

GP1BA p.Ser378Phe Uncertain significance ★ ⚠ same residue
GP1BA p.Ala172Val Pathogenic ★★ ⚠ same condition
GP1BA p.Gly249Val Pathogenic/Likely pathogenic ★★ same condition
GP1BA p.Leu83Phe Likely pathogenic ★★ ⚠ same condition
GP1BA p.Met255Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
GP1BA p.Val31Glu Uncertain significance ★★ ⚠ same condition
GP1BA p.Asn198Ser Likely pathogenic ★ same condition
GP1BA p.Cys33Gly Likely pathogenic ★ 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/gp1ba-p-ser378pro (accessed [today's date]).

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