Is GPAA1 p.Pro410Ser (c.1228C>T) pathogenic?

GPAA1 p.Pro410Ser (c.1228C>T) is classified Uncertain significance in GPAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.0661); Absent from gnomAD v4.1.

How common is GPAA1 p.Pro410Ser (c.1228C>T) in the general population?

GPAA1 p.Pro410Ser (c.1228C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPAA1 p.Pro410Ser (c.1228C>T)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

GPAA1 p.Pro410Ser

c.1228C>T · rs2537317307 · VCV2069448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.57	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 -0.44	GERP -3.7
Regional constraint	o/e 0.95	unconstrained · MANE · 3,391 bp · p 0.14 · regional, not allelic
Overall
CADD	0.104	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: GPAA1
Protein: p.Pro410Ser
Coding: c.1228C>T
MANE Select: NM_003801
dbSNP: rs2537317307
Type: single nucleotide variant
Location: chr8:144085106 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.48 · 4 PDB

Full GPAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPAA1 c.1165-1C>T Likely pathogenic ★★ same type
GPAA1 c.366+1G>A Likely pathogenic ★★ same type
GPAA1 c.616+1G>T Likely pathogenic ★★ same type
GPAA1 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same type
GPAA1 p.Leu291Pro Likely pathogenic ★★ same type
GPAA1 p.Ser419Ter Pathogenic/Likely pathogenic ★★ same type
GPAA1 c.1164+1A>G Uncertain significance ★★ same type
GPAA1 c.1451+5G>A Uncertain significance ★★ 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/gpaa1-p-pro410ser (accessed [today's date]).

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