Is AGAP2 p.Asp990Val (c.2969A>T) pathogenic?

AGAP2 p.Asp990Val (c.2969A>T) is classified Uncertain significance in AGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). Very rare (popmax 8.48e-05%, nfe).

How common is AGAP2 p.Asp990Val (c.2969A>T) in the general population?

AGAP2 p.Asp990Val (c.2969A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

AGAP2 p.Asp990Val

c.2969A>T · rs2540839471 · VCV2309833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.248	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 124 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,848 alleles

Overall 6.84e-05% 1/1,461,580 alleles · very rare

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.Asp990Val
Coding: c.2969A>T
MANE Select: NM_001122772
dbSNP: rs2540839471
Type: single nucleotide variant
Location: chr12:57727471 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 60.04 · 3 PDB
Residue 990: the arf-gap domain

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-asp990val (accessed [today's date]).

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