Is AGAP1 p.Ile712Val (c.2134A>G) pathogenic?

AGAP1 p.Ile712Val (c.2134A>G) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.6108); Very rare (popmax 0.000848%, nfe).

How common is AGAP1 p.Ile712Val (c.2134A>G) in the general population?

AGAP1 p.Ile712Val (c.2134A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about AGAP1 p.Ile712Val (c.2134A>G)?

AlphaMissense predicts likely pathogenic (score 0.6108) — an in-silico prediction, not a clinical call.

AGAP1 p.Ile712Val

c.2134A>G · rs761131808 · VCV2472327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6108	likely pathogenic
REVEL	0.451	indeterminate
SaProt	LLR -10.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000848% European (non-Finnish) · 10/1,178,984 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,612,384 alleles · very rare exomes 11/1,460,074 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,400
European (non-Finnish)grpmax	0.000848%	117,898

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile712Val
Coding: c.2134A>G
MANE Select: NM_001037131
dbSNP: rs761131808
Type: single nucleotide variant
Location: chr2:236120211 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 712: the arf-gap domain

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

Similar variants

AGAP1 p.Ile712fs 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-ile712val (accessed [today's date]).

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