Is GP1BA p.Ser515Phe (c.1544C>T) pathogenic?

GP1BA p.Ser515Phe (c.1544C>T) is classified Uncertain significance in GP1BA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1308); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with GP1BA p.Ser515Phe (c.1544C>T)?

GP1BA p.Ser515Phe (c.1544C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GP1BA p.Ser515Phe (c.1544C>T) in the general population?

GP1BA p.Ser515Phe (c.1544C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about GP1BA p.Ser515Phe (c.1544C>T)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

GP1BA p.Ser515Phe

c.1544C>T · VCV3281997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.36	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 0.8	GERP -2
Regional constraint	o/e 1.00	unconstrained · MANE · 595 bp · p 0.98 · regional, not allelic
Overall
CADD	8.785	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 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,750 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
East Asian	0.00223%	44,896
European (non-Finnish)	0.00017%	589,953

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.Ser515Phe
Coding: c.1544C>T
MANE Select: NM_000173
Type: single nucleotide variant
Location: chr17:4934148 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB

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

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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
GP1BA p.Asp518Glu 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-ser515phe (accessed [today's date]).

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