Is AGAP1 p.Gln586Arg (c.1757A>G) pathogenic?

AGAP1 p.Gln586Arg (c.1757A>G) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely pathogenic (0.8386); Very rare (popmax 0.00305%, nfe).

How common is AGAP1 p.Gln586Arg (c.1757A>G) in the general population?

AGAP1 p.Gln586Arg (c.1757A>G) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about AGAP1 p.Gln586Arg (c.1757A>G)?

AlphaMissense predicts likely pathogenic (score 0.8386) — an in-silico prediction, not a clinical call.

AGAP1 p.Gln586Arg

c.1757A>G · rs778746496 · VCV2186302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8386	likely pathogenic
REVEL	0.241	benign-leaning
SaProt	LLR -13.89	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,180,038 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00229% 37/1,614,234 alleles · very rare exomes 37/1,461,890 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00305%	32,779
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Gln586Arg
Coding: c.1757A>G
MANE Select: NM_001037131
dbSNP: rs778746496
Type: single nucleotide variant
Location: chr2:236036672 (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.Gln586= Likely benign ★ 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-gln586arg (accessed [today's date]).

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