Is AGAP1 p.Ile680Val (c.2038A>G) pathogenic?

AGAP1 p.Ile680Val (c.2038A>G) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.1111); Very rare (popmax 8.47e-05%, nfe).

How common is AGAP1 p.Ile680Val (c.2038A>G) in the general population?

AGAP1 p.Ile680Val (c.2038A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AGAP1 p.Ile680Val (c.2038A>G)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

AGAP1 p.Ile680Val

c.2038A>G · rs2057820490 · VCV3093593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP -0.25, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,058 alleles

Overall 6.2e-05% 1/1,614,110 alleles · very rare exomes 0/1,461,894 · genomes 1/152,216 · 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.Ile680Val
Coding: c.2038A>G
MANE Select: NM_001037131
dbSNP: rs2057820490
Type: single nucleotide variant
Location: chr2:236049205 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 680: the arf-gap domain

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

Similar variants

AGAP1 p.Ile680= 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-ile680val (accessed [today's date]).

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