Is AGAP3 p.Ser396Ile (c.1187G>T) pathogenic?

AGAP3 p.Ser396Ile (c.1187G>T) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely benign (0.2603); Very rare (popmax 0.005%, amr).

How common is AGAP3 p.Ser396Ile (c.1187G>T) in the general population?

AGAP3 p.Ser396Ile (c.1187G>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about AGAP3 p.Ser396Ile (c.1187G>T)?

AlphaMissense predicts likely benign (score 0.2603) — an in-silico prediction, not a clinical call.

AGAP3 p.Ser396Ile

c.1187G>T · VCV4022701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2603 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2603	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -11.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP -1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 84 bp · p 0.26 · regional, not allelic
Overall
CADD	23.3	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 S360I vs ClinVar S396I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,014 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000411% 6/1,459,264 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,005
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00017%	589,964

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AGAP3
Protein: p.Ser396Ile
Coding: c.1187G>T
MANE Select: NM_031946
Type: single nucleotide variant
Location: chr7:151123852 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB
Residue 396: 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-ser396ile (accessed [today's date]).

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