Is GP1BA p.Phe207Cys (c.620T>G) pathogenic?

GP1BA p.Phe207Cys (c.620T>G) is classified Uncertain significance in GP1BA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely pathogenic (0.9392); Absent from gnomAD v4.1.

How common is GP1BA p.Phe207Cys (c.620T>G) in the general population?

GP1BA p.Phe207Cys (c.620T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GP1BA p.Phe207Cys (c.620T>G)?

AlphaMissense predicts likely pathogenic (score 0.9392) — an in-silico prediction, not a clinical call.

GP1BA p.Phe207Cys

c.620T>G · VCV3380458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9392 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9392	likely pathogenic · top 4% in GP1BA
REVEL	0.458	indeterminate
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,223 bp · p 0.011 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe207Cys
Coding: c.620T>G
MANE Select: NM_000173
Type: single nucleotide variant
Location: chr17:4933224 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB
Residue 207: a turn

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

Similar variants

GP1BA p.Phe207Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
GP1BA p.Phe207= Likely benign ★ same residue
GP1BA p.Cys225Arg Likely pathogenic ★★★ same type
GP1BA p.Cys81Arg Pathogenic ★★★ same type
GP1BA p.Gln346Ter Likely pathogenic ★★★ same type
GP1BA p.Glu347Ter Likely pathogenic ★★★ same type
GP1BA p.Leu145Pro Likely pathogenic ★★★ same type
GP1BA p.Ser267Ter 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/gp1ba-p-phe207cys (accessed [today's date]).

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