Is ARAP1 p.Lys1032Arg (c.3095A>G) pathogenic?

ARAP1 p.Lys1032Arg (c.3095A>G) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.7873); Very rare (popmax 0.0011%, sas).

How common is ARAP1 p.Lys1032Arg (c.3095A>G) in the general population?

ARAP1 p.Lys1032Arg (c.3095A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ARAP1 p.Lys1032Arg (c.3095A>G)?

AlphaMissense predicts likely pathogenic (score 0.7873) — an in-silico prediction, not a clinical call.

ARAP1 p.Lys1032Arg

c.3095A>G · VCV4129778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7873	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -11.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,408 bp · p 0.49 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,088 alleles

Overall 6.86e-05% 1/1,458,002 alleles · very rare

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.Lys1032Arg
Coding: c.3095A>G
MANE Select: NM_001040118
Type: single nucleotide variant
Location: chr11:72697054 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB
Residue 1032: the rho-gap domain

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

Similar variants

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
ARAP1 p.Ala1389Thr 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-lys1032arg (accessed [today's date]).

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