Is AGAP3 p.Pro298Ser (c.892C>T) pathogenic?

AGAP3 p.Pro298Ser (c.892C>T) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.5706); Absent from gnomAD v4.1.

How common is AGAP3 p.Pro298Ser (c.892C>T) in the general population?

AGAP3 p.Pro298Ser (c.892C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP3 p.Pro298Ser (c.892C>T)?

AlphaMissense predicts likely pathogenic (score 0.5706) — an in-silico prediction, not a clinical call.

AGAP3 p.Pro298Ser

c.892C>T · VCV4638826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5706 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5706	likely pathogenic
REVEL	0.187	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.51, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 5,261 bp · p 0.0098 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P262S vs ClinVar P298S) — verify the residue.

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: AGAP3
Protein: p.Pro298Ser
Coding: c.892C>T
MANE Select: NM_031946
Type: single nucleotide variant
Location: chr7:151118555 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB
Residue 298: the 'small gtpase-like' region

Full AGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP3 p.Arg252= Benign ★★ same type
AGAP3 p.Ala314Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala324Val Uncertain significance ★ ⚠ same type
AGAP3 p.Ala331Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala389Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala470Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala62Val Uncertain significance ★ ⚠ same type
AGAP3 p.Ala67Val 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/agap3-p-pro298ser (accessed [today's date]).

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