Is AGAP6 p.Ala596Pro (c.1786G>C) pathogenic?

AGAP6 p.Ala596Pro (c.1786G>C) is classified Uncertain significance in AGAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.4554); Absent from gnomAD v4.1.

How common is AGAP6 p.Ala596Pro (c.1786G>C) in the general population?

AGAP6 p.Ala596Pro (c.1786G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP6 p.Ala596Pro (c.1786G>C)?

AlphaMissense predicts ambiguous (score 0.4554) — an in-silico prediction, not a clinical call.

AGAP6 p.Ala596Pro

c.1786G>C · VCV4638881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4554 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4554	ambiguous · top 8% in AGAP6
REVEL	0.113	moderately benign-leaning
SaProt	LLR -14.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	phastCons 0.91
Regional constraint	o/e 0.41	unconstrained · MANE · 189 bp · p 8.7e-08 · regional, not allelic
Overall
CADD	9.633	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 A573P vs ClinVar A596P) — 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: AGAP6
Protein: p.Ala596Pro
Coding: c.1786G>C
MANE Select: NM_001077665
Type: single nucleotide variant
Location: chr10:50009911 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.73

Full AGAP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP6 p.Ala105Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala109Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala135Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala180Gly Uncertain significance ★ ⚠ same type
AGAP6 p.Ala425Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala433Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala43Ser Uncertain significance ★ ⚠ same type
AGAP6 p.Ala444Pro 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/agap6-p-ala596pro (accessed [today's date]).

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