Is ARAP3 p.Pro96Leu (c.287C>T) pathogenic?

ARAP3 p.Pro96Leu (c.287C>T) is classified Uncertain significance in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: ambiguous (0.3477); Very rare (popmax 0.00668%, amr).

How common is ARAP3 p.Pro96Leu (c.287C>T) in the general population?

ARAP3 p.Pro96Leu (c.287C>T) is very rare (popmax 0.00668%, amr) (gnomAD).

What do computational predictors say about ARAP3 p.Pro96Leu (c.287C>T)?

AlphaMissense predicts ambiguous (score 0.3477) — an in-silico prediction, not a clinical call.

ARAP3 p.Pro96Leu

c.287C>T · rs764484654 · VCV2220906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3477	ambiguous
REVEL	0.095	moderately benign-leaning
SaProt	LLR -9.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,347 bp · p 0.061 · regional, not allelic
Overall
CADD	26.2	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 0.00668% Admixed American · 4/59,892 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00391% 63/1,611,192 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00668%	14,973
Remaining individualsnot grpmax-eligible	0.00481%	20,782
European (non-Finnish)	0.0045%	22,228
African / African-American	0.00267%	37,419
Finnishnot grpmax-eligible	0.00156%	63,906

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.Pro96Leu
Coding: c.287C>T
MANE Select: NM_022481
dbSNP: rs764484654
Type: single nucleotide variant
Location: chr5:141680200 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB
Residue 96: 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-pro96leu (accessed [today's date]).

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