Is AGAP1 p.Gln586= (c.1758G>A) pathogenic?

AGAP1 p.Gln586= (c.1758G>A) is classified Likely benign in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). Very rare (popmax 0.00195%, nfe).

How common is AGAP1 p.Gln586= (c.1758G>A) in the general population?

AGAP1 p.Gln586= (c.1758G>A) is very rare (popmax 0.00195%, nfe) (gnomAD).

AGAP1 p.Gln586=

c.1758G>A · VCV3701825

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.201	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,180,048 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00142% 23/1,614,114 alleles · very rare exomes 21/1,461,888 · genomes 2/152,226 · joint denominator

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: AGAP1
Protein: p.Gln586=
Coding: c.1758G>A
MANE Select: NM_001037131
Type: single nucleotide variant
Location: chr2:236036673 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 586: the ph domain

Full AGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP1 p.Gln586Arg Uncertain significance ★ ⚠ same residue
AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala570Gly Uncertain significance ★★ same type
AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg696Trp 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/agap1-p-gln586 (accessed [today's date]).

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