Is ARAP3 p.Gln90Pro (c.269A>C) pathogenic?

ARAP3 p.Gln90Pro (c.269A>C) is classified Uncertain significance in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.0594); Ultra-rare (popmax 0.031%, nfe).

How common is ARAP3 p.Gln90Pro (c.269A>C) in the general population?

ARAP3 p.Gln90Pro (c.269A>C) is ultra-rare (popmax 0.031%, nfe) (gnomAD).

What do computational predictors say about ARAP3 p.Gln90Pro (c.269A>C)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

ARAP3 p.Gln90Pro

c.269A>C · rs138194565 · VCV2349191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.031%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -4.96	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 4.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,347 bp · p 0.061 · regional, not allelic
Overall
CADD	15.61	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 0.031% European (non-Finnish) · 366/1,179,506 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0238% 384/1,612,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.031%	3,223
Remaining individualsnot grpmax-eligible	0.0224%	4,460
African / African-American	0.00401%	24,910
Admixed American	0.00167%	59,924

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.Gln90Pro
Coding: c.269A>C
MANE Select: NM_022481
dbSNP: rs138194565
Type: single nucleotide variant
Location: chr5:141680218 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB
Residue 90: the 'disordered' region

Full ARAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP3 p.Ala1045Val Uncertain significance ★ same type
ARAP3 p.Ala10Thr Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1159Val Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1276Ser Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1342Thr Uncertain significance ★ ⚠ same type
ARAP3 p.Ala216Asp Uncertain significance ★ ⚠ same type
ARAP3 p.Ala22Val Uncertain significance ★ ⚠ same type
ARAP3 p.Ala36Thr 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/arap3-p-gln90pro (accessed [today's date]).

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