Is ARAP3 p.Arg511His (c.1532G>A) pathogenic?

ARAP3 p.Arg511His (c.1532G>A) is classified Uncertain significance in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0869); Very rare (popmax 0.00769%, sas).

How common is ARAP3 p.Arg511His (c.1532G>A) in the general population?

ARAP3 p.Arg511His (c.1532G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about ARAP3 p.Arg511His (c.1532G>A)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

ARAP3 p.Arg511His

c.1532G>A · rs781686907 · VCV2217046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.53	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 4.9	GERP -5.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,347 bp · p 0.061 · regional, not allelic
Overall
CADD	23.9	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 0.00769% South Asian · 7/91,086 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00116% 17/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Admixed American	0.00167%	60,028
European (non-Finnish)	0.000763%	131,113

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: ARAP3
Protein: p.Arg511His
Coding: c.1532G>A
MANE Select: NM_022481
dbSNP: rs781686907
Type: single nucleotide variant
Location: chr5:141672155 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB
Residue 511: the arf-gap domain

Full ARAP3 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/arap3-p-arg511his (accessed [today's date]).

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