Is GP1BA p.Ser378Phe (c.1133C>T) pathogenic?

GP1BA p.Ser378Phe (c.1133C>T) is classified Uncertain significance in GP1BA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.1387); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GP1BA p.Ser378Phe (c.1133C>T)?

GP1BA p.Ser378Phe (c.1133C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GP1BA p.Ser378Phe (c.1133C>T) in the general population?

GP1BA p.Ser378Phe (c.1133C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GP1BA p.Ser378Phe (c.1133C>T)?

AlphaMissense predicts likely benign (score 0.1387) — an in-silico prediction, not a clinical call.

GP1BA p.Ser378Phe

c.1133C>T · rs2507593553 · VCV2480367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1387 · 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	0.1387	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -8.66	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 -0.27	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 1,223 bp · p 0.011 · regional, not allelic
Overall
CADD	6.682	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

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: GP1BA
Protein: p.Ser378Phe
Coding: c.1133C>T
MANE Select: NM_000173
dbSNP: rs2507593553
Type: single nucleotide variant
Location: chr17:4933737 (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

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

Similar variants

GP1BA p.Ser378Pro Uncertain significance ⚠ same residue
GP1BA p.Ala318Thr Uncertain significance ★★ ⚠ same condition
GP1BA p.Arg586Gln Uncertain significance ★★ ⚠ same condition
GP1BA p.Arg592Gln Uncertain significance ★★ ⚠ same condition
GP1BA p.Arg592Trp Uncertain significance ★★ ⚠ same condition
GP1BA p.Arg635His Uncertain significance ★★ ⚠ same condition
GP1BA p.Asp238Asn Uncertain significance ★★ ⚠ same condition
GP1BA p.Asp285Ala 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/gp1ba-p-ser378phe (accessed [today's date]).

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