Is AGAP3 p.Ser536Pro (c.1606T>C) pathogenic?

AGAP3 p.Ser536Pro (c.1606T>C) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1874); Absent from gnomAD v4.1.

How common is AGAP3 p.Ser536Pro (c.1606T>C) in the general population?

AGAP3 p.Ser536Pro (c.1606T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP3 p.Ser536Pro (c.1606T>C)?

AlphaMissense predicts likely benign (score 0.1874) — an in-silico prediction, not a clinical call.

AGAP3 p.Ser536Pro

c.1606T>C · VCV4249668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1874	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -12.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 5,547 bp · p 0.38 · regional, not allelic
Overall
CADD	26.3	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 S500P vs ClinVar S536P) — 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.Ser536Pro
Coding: c.1606T>C
MANE Select: NM_031946
Type: single nucleotide variant
Location: chr7:151138253 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB
Residue 536: the 'disordered' region; the ph domain

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-ser536pro (accessed [today's date]).

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