Is AGAP1 p.Arg696Trp (c.2086C>T) pathogenic?

AGAP1 p.Arg696Trp (c.2086C>T) is classified Uncertain significance in AGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-02). AlphaMissense: likely benign (0.1045); Ultra-rare (popmax 0.06%, afr).

How common is AGAP1 p.Arg696Trp (c.2086C>T) in the general population?

AGAP1 p.Arg696Trp (c.2086C>T) is ultra-rare (popmax 0.06%, afr) (gnomAD).

What do computational predictors say about AGAP1 p.Arg696Trp (c.2086C>T)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

AGAP1 p.Arg696Trp

c.2086C>T · VCV3505173

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.469	indeterminate
SaProt	LLR -13.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	32.0	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 0.06% African / African-American · 45/75,036 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.00719% 116/1,614,106 alleles · ultra-rare exomes 87/1,461,814 · genomes 29/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.06%	1,667
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00988%	10,118
Admixed American	0.00666%	15,007
European (non-Finnish)	0.00407%	24,583

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.Arg696Trp
Coding: c.2086C>T
MANE Select: NM_001037131
Type: single nucleotide variant
Location: chr2:236049253 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 696: the arf-gap domain

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

Similar variants

AGAP1 p.Arg696Gln Uncertain significance ★ ⚠ same residue
AGAP1 p.Arg696Leu 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

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-arg696trp (accessed [today's date]).

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