Is AGAP5 p.Ala596Thr (c.1786G>A) pathogenic?

AGAP5 p.Ala596Thr (c.1786G>A) is classified Uncertain significance in AGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.0955); Ultra-rare (popmax 0.0528%, sas).

How common is AGAP5 p.Ala596Thr (c.1786G>A) in the general population?

AGAP5 p.Ala596Thr (c.1786G>A) is ultra-rare (popmax 0.0528%, sas) (gnomAD).

What do computational predictors say about AGAP5 p.Ala596Thr (c.1786G>A)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

AGAP5 p.Ala596Thr

c.1786G>A · rs1335706138 · VCV2385787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0528%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -10.00	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 1.5	GERP -0.3, phastCons 0.07
Regional constraint	o/e 0.18	constrained · MANE · 429 bp · p 2.1e-28 · regional, not allelic
Overall
CADD	8.855	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

Grpmax group 0.0528% South Asian · 48/90,986 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00521% 84/1,612,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0528%	1,896
Admixed American	0.00833%	12,002
European (non-Finnish)	0.00263%	38,058

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: AGAP5
Protein: p.Ala596Thr
Coding: c.1786G>A
MANE Select: NM_001144000
dbSNP: rs1335706138
Type: single nucleotide variant
Location: chr10:73674874 (GRCh38)
Gene constraint: LOEUF 0.717 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.80

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.Ala608Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala608Val Uncertain significance ★ ⚠ same type
AGAP5 p.Ala660Gly 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-ala596thr (accessed [today's date]).

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