Is AGAP2 p.Pro326= (c.978G>C) pathogenic?

AGAP2 p.Pro326= (c.978G>C) is classified Likely benign in AGAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-16). Rare (popmax 0.284%, afr); Associated with AGAP2-related disorder.

What condition is associated with AGAP2 p.Pro326= (c.978G>C)?

AGAP2 p.Pro326= (c.978G>C) is associated with AGAP2-related disorder (ClinVar).

How common is AGAP2 p.Pro326= (c.978G>C) in the general population?

AGAP2 p.Pro326= (c.978G>C) is rare (popmax 0.284%, afr) (gnomAD).

AGAP2 p.Pro326=

c.978G>C · rs542194963 · VCV3044506

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.284%, afr)

Conditions

AGAP2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3.5
Overall
CADD	2.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.284% African / African-American · 213/75,054 alleles

Filtering AF 0.252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.24%

Overall 0.0152% 245/1,613,284 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.284%	352
Remaining individualsnot grpmax-eligible	0.00801%	12,484
Admixed American	0.005%	19,995
European (non-Finnish)	0.00203%	49,156

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: AGAP2
Protein: p.Pro326=
Coding: c.978G>C
MANE Select: NM_001122772
dbSNP: rs542194963
Type: single nucleotide variant
Location: chr12:57737269 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 60.04 · 3 PDB
Residue 326: the 'interaction with plcg1' region; the 'disordered' region

Full AGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AGAP2-related disorder

Similar variants

AGAP2 p.Gly462Arg Uncertain significance ★ same condition
AGAP2 p.Val881Ala Uncertain significance ★ same condition
AGAP2 p.Arg984Leu Uncertain significance same condition
AGAP2 p.Ala11Val Likely benign same condition
AGAP2 p.Gln598= Likely benign same condition
AGAP2 p.Glu438Gln Benign same condition
AGAP2 p.Gly507Ser Likely benign same condition
AGAP2 p.His1096= Likely benign same condition

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/agap2-p-pro326 (accessed [today's date]).

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