Is AGAP3 p.Pro58Ser (c.172C>T) pathogenic?

AGAP3 p.Pro58Ser (c.172C>T) is classified Uncertain significance in AGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0582); Ultra-rare (popmax 0.0415%, afr).

How common is AGAP3 p.Pro58Ser (c.172C>T) in the general population?

AGAP3 p.Pro58Ser (c.172C>T) is ultra-rare (popmax 0.0415%, afr) (gnomAD).

What do computational predictors say about AGAP3 p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

AGAP3 p.Pro58Ser

c.172C>T · rs750348682 · VCV2518248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0415%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -7.17	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 2.1	GERP -0.52, phastCons 0.98
Regional constraint	o/e 0.75	unconstrained · MANE · 211 bp · p 0.022 · regional, not allelic
Overall
CADD	22.7	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 P22S vs ClinVar P58S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0415% African / African-American · 30/72,316 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00221% 35/1,580,464 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0415%	2,411
Admixed American	0.00532%	18,787
Remaining individualsnot grpmax-eligible	0.00329%	30,366

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.Pro58Ser
Coding: c.172C>T
MANE Select: NM_031946
dbSNP: rs750348682
Type: single nucleotide variant
Location: chr7:151086913 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 1 PDB

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

Similar variants

AGAP3 p.Pro58Leu Uncertain significance ★ ⚠ 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-pro58ser (accessed [today's date]).

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