Is AGAP3 p.Met552Val (c.1654A>G) pathogenic?

AGAP3 p.Met552Val (c.1654A>G) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely benign (0.0575); Rare (popmax 0.148%, mid).

How common is AGAP3 p.Met552Val (c.1654A>G) in the general population?

AGAP3 p.Met552Val (c.1654A>G) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about AGAP3 p.Met552Val (c.1654A>G)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

AGAP3 p.Met552Val

c.1654A>G · rs758585736 · VCV2466929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -4.85	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 1	GERP -3.1, phastCons 0.033
Regional constraint	o/e 1.07	unconstrained · MANE · 5,547 bp · p 0.38 · regional, not allelic
Overall
CADD	8.158	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M516V vs ClinVar M552V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,076 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.00409% 66/1,611,744 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	675
African / African-American	0.0147%	6,812
Remaining individualsnot grpmax-eligible	0.00641%	15,599
South Asian	0.0055%	18,179
Admixed American	0.00501%	19,967
European (non-Finnish)	0.00288%	34,683

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: AGAP3
Protein: p.Met552Val
Coding: c.1654A>G
MANE Select: NM_031946
dbSNP: rs758585736
Type: single nucleotide variant
Location: chr7:151138301 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB
Residue 552: the 'disordered' region; the ph domain

Full AGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP3 p.Met552Thr Likely benign ★ same residue
AGAP3 p.Arg252= Benign ★★ same type
AGAP3 p.Ala314Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala324Val Uncertain significance ★ ⚠ same type
AGAP3 p.Ala331Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala389Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala470Thr Uncertain significance ★ ⚠ same type
AGAP3 p.Ala62Val 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/agap3-p-met552val (accessed [today's date]).

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