Is ARAP1 p.Arg864Trp (c.2590C>T) pathogenic?

ARAP1 p.Arg864Trp (c.2590C>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely pathogenic (0.5925); Ultra-rare (popmax 0.0224%, eas).

How common is ARAP1 p.Arg864Trp (c.2590C>T) in the general population?

ARAP1 p.Arg864Trp (c.2590C>T) is ultra-rare (popmax 0.0224%, eas) (gnomAD).

What do computational predictors say about ARAP1 p.Arg864Trp (c.2590C>T)?

AlphaMissense predicts likely pathogenic (score 0.5925) — an in-silico prediction, not a clinical call.

ARAP1 p.Arg864Trp

c.2590C>T · rs577374952 · VCV3128201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5925 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5925	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -11.83	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 15 kb · p 7.9e-09 · regional, not allelic
Overall
CADD	27.1	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 0.0224% East Asian · 10/44,630 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00921%

Overall 0.00274% 44/1,606,550 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0224%	4,463
Middle Eastern	0.0165%	6,066
Remaining individualsnot grpmax-eligible	0.00482%	20,735
African / African-American	0.00401%	24,943
European (non-Finnish)	0.00221%	45,272
Finnishnot grpmax-eligible	0.00158%	63,132

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: ARAP1
Protein: p.Arg864Trp
Coding: c.2590C>T
MANE Select: NM_001040118
dbSNP: rs577374952
Type: single nucleotide variant
Location: chr11:72698058 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB

Full ARAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP1 p.Arg864Gln Uncertain significance ★ ⚠ same residue
ARAP1 p.Gln1047Glu Benign ★★ same type
ARAP1 p.Pro1039= Benign ★★ same type
ARAP1 p.Pro254Leu Benign ★★ same type
ARAP1 p.Val1408Met Benign ★★ ⚠ same type
ARAP1 p.Ala1046Ser Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1124Thr Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1199Thr 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/arap1-p-arg864trp (accessed [today's date]).

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