Is AGAP1 p.Lys73Arg (c.218A>G) pathogenic?

AGAP1 p.Lys73Arg (c.218A>G) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.1484); Very rare (popmax 0.00167%, amr).

How common is AGAP1 p.Lys73Arg (c.218A>G) in the general population?

AGAP1 p.Lys73Arg (c.218A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AGAP1 p.Lys73Arg (c.218A>G)?

AlphaMissense predicts likely benign (score 0.1484) — an in-silico prediction, not a clinical call.

AGAP1 p.Lys73Arg

c.218A>G · rs752777269 · VCV2320125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1484	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	28.9	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 0.00167% Admixed American · 1/59,988 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,878 alleles · very rare exomes 4/1,461,810 · genomes 1/152,068 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
European (non-Finnish)	0.000339%	294,992

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: AGAP1
Protein: p.Lys73Arg
Coding: c.218A>G
MANE Select: NM_001037131
dbSNP: rs752777269
Type: single nucleotide variant
Location: chr2:235709233 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 73: the gld domain; a β-strand; the 'small gtpase-like' region

Full AGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/agap1-p-lys73arg (accessed [today's date]).

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