Is AGAP3 p.Ile69Val (c.205A>G) pathogenic?

AGAP3 p.Ile69Val (c.205A>G) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.7969); Absent from gnomAD v4.1.

How common is AGAP3 p.Ile69Val (c.205A>G) in the general population?

AGAP3 p.Ile69Val (c.205A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP3 p.Ile69Val (c.205A>G)?

AlphaMissense predicts likely pathogenic (score 0.7969) — an in-silico prediction, not a clinical call.

AGAP3 p.Ile69Val

c.205A>G · VCV4249660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7969	likely pathogenic
REVEL	0.446	indeterminate
SaProt	LLR -10.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.69, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 211 bp · p 0.022 · regional, not allelic
Overall
CADD	24.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I33V vs ClinVar I69V) — 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.Ile69Val
Coding: c.205A>G
MANE Select: NM_031946
Type: single nucleotide variant
Location: chr7:151086946 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB

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-ile69val (accessed [today's date]).

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