Is AGAP5 p.Ser547Arg (c.1639A>C) pathogenic?

AGAP5 p.Ser547Arg (c.1639A>C) is classified Uncertain significance in AGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2582); Very rare (popmax 0.00835%, amr).

How common is AGAP5 p.Ser547Arg (c.1639A>C) in the general population?

AGAP5 p.Ser547Arg (c.1639A>C) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about AGAP5 p.Ser547Arg (c.1639A>C)?

AlphaMissense predicts likely benign (score 0.2582) — an in-silico prediction, not a clinical call.

AGAP5 p.Ser547Arg

c.1639A>C · VCV3275292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2582	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -7.66	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 0.37	GERP -2.8, phastCons 0.003
Regional constraint	o/e 0.18	constrained · MANE · 429 bp · p 2.1e-28 · regional, not allelic
Overall
CADD	18.03	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00835% Admixed American · 5/59,906 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00298% 48/1,612,384 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,981
European (non-Finnish)	0.00348%	28,772
Remaining individualsnot grpmax-eligible	0.0016%	62,382
African / African-American	0.00134%	74,810

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.Ser547Arg
Coding: c.1639A>C
MANE Select: NM_001144000
Type: single nucleotide variant
Location: chr10:73675021 (GRCh38)
Gene constraint: LOEUF 0.717 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.80
Residue 547: the arf-gap 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-ser547arg (accessed [today's date]).

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