Is AGAP5 p.Ser293Arg (c.877A>C) pathogenic?

AGAP5 p.Ser293Arg (c.877A>C) is classified Uncertain significance in AGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely pathogenic (0.591); Absent from gnomAD v4.1.

How common is AGAP5 p.Ser293Arg (c.877A>C) in the general population?

AGAP5 p.Ser293Arg (c.877A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGAP5 p.Ser293Arg (c.877A>C)?

AlphaMissense predicts likely pathogenic (score 0.591) — an in-silico prediction, not a clinical call.

AGAP5 p.Ser293Arg

c.877A>C · VCV3275355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.591	likely pathogenic · top 5% in AGAP5
REVEL	0.339	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.014
Regional constraint	o/e 0.08	constrained · MANE · 269 bp · p 4e-22 · regional, not allelic
Overall
CADD	18.34	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGAP5
Protein: p.Ser293Arg
Coding: c.877A>C
MANE Select: NM_001144000
Type: single nucleotide variant
Location: chr10:73675783 (GRCh38)
Gene constraint: LOEUF 0.717 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.80
Residue 293: the ph domain

Full AGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP5 p.Ala195Val Uncertain significance ★ ⚠ same type
AGAP5 p.Ala397Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala41Glu Uncertain significance ★ ⚠ same type
AGAP5 p.Ala43Val Uncertain significance ★ ⚠ same type
AGAP5 p.Ala444Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala596Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala608Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala608Val 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/agap5-p-ser293arg (accessed [today's date]).

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