Is AGAP4 p.Ser518Pro (c.1552T>C) pathogenic?

AGAP4 p.Ser518Pro (c.1552T>C) is classified Uncertain significance in AGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.3292); Absent from gnomAD v4.1.

How common is AGAP4 p.Ser518Pro (c.1552T>C) in the general population?

AGAP4 p.Ser518Pro (c.1552T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP4 p.Ser518Pro (c.1552T>C)?

AlphaMissense predicts likely benign (score 0.3292) — an in-silico prediction, not a clinical call.

AGAP4 p.Ser518Pro

c.1552T>C · VCV3505558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3292 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,194)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3292	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -12.59	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	phastCons 0.97
Regional constraint	o/e 0.15	constrained · MANE · 470 bp · p 4.2e-35 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S495P vs ClinVar S518P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,194). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGAP4
Protein: p.Ser518Pro
Coding: c.1552T>C
MANE Select: NM_001276343
Type: single nucleotide variant
Location: chr10:45826424 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 63.70
Residue 518: the arf-gap domain

Full AGAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP4 p.Ala41Thr Uncertain significance ★ ⚠ same type
AGAP4 p.Ala464Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala466Ser Uncertain significance ★ ⚠ same type
AGAP4 p.Ala627Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala640Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala655Val Uncertain significance ★ ⚠ same type
AGAP4 p.Arg137Leu Uncertain significance ★ ⚠ same type
AGAP4 p.Arg246Gln 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/agap4-p-ser518pro (accessed [today's date]).

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