Is AGAP3 p.Arg252= (c.756C>T) pathogenic?

AGAP3 p.Arg252= (c.756C>T) is classified Benign in AGAP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-09-19). Common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele.

AGAP3 p.Arg252=

Q: How common is AGAP3 p.Arg252= (c.756C>T) in the general population?

AGAP3 p.Arg252= (c.756C>T) is common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.756C>T · rs73476760 · VCV1279697

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.6%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3.1, phastCons 0.2
Overall
CADD	14.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.6% African / African-American · 6,452/75,002 alleles

Filtering AF 8.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.36%

Overall 0.488% 7,867/1,613,276 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.6%	12
Admixed American	0.917%	109
Remaining individualsnot grpmax-eligible	0.584%	171
Middle Eastern	0.38%	263
European (non-Finnish)	0.0383%	2,609
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
South Asian	0.0176%	5,692

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.Arg252=
Coding: c.756C>T
MANE Select: NM_031946
dbSNP: rs73476760
Type: single nucleotide variant
Location: chr7:151118259 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB
Residue 252: the gld domain; an α-helix; the 'small gtpase-like' region

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

Similar variants

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
AGAP3 p.Ala67Val Uncertain significance ★ ⚠ same type
AGAP3 p.Ala709Thr 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-arg252 (accessed [today's date]).

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