Is AGAP2 p.Val733Ile (c.2197G>A) pathogenic?

AGAP2 p.Val733Ile (c.2197G>A) is classified Uncertain significance in AGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). Absent from gnomAD v4.1.

How common is AGAP2 p.Val733Ile (c.2197G>A) in the general population?

AGAP2 p.Val733Ile (c.2197G>A) is absent from gnomAD v4.1 (gnomAD).

AGAP2 p.Val733Ile

c.2197G>A · VCV4249444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,150)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.399	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 675 bp · p 4.8e-08 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,150). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGAP2
Protein: p.Val733Ile
Coding: c.2197G>A
MANE Select: NM_001122772
Type: single nucleotide variant
Location: chr12:57730902 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 60.04 · 3 PDB
Residue 733: the ph domain; a β-strand

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

Similar variants

AGAP2 p.Leu210Gln Uncertain significance ★★ same type
AGAP2 p.Val527= Benign ★★ same type
AGAP2 p.Ala1045Glu Uncertain significance ★ same type
AGAP2 p.Ala1156Thr Uncertain significance ★ same type
AGAP2 p.Ala1161Val Uncertain significance ★ same type
AGAP2 p.Ala116Asp Uncertain significance ★ same type
AGAP2 p.Ala228Val Uncertain significance ★ same type
AGAP2 p.Ala237Thr 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/agap2-p-val733ile (accessed [today's date]).

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