Is ARAP3 p.His386Pro (c.1157A>C) pathogenic?

ARAP3 p.His386Pro (c.1157A>C) is classified Uncertain significance in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.0717); Very rare (popmax 0.00536%, afr).

How common is ARAP3 p.His386Pro (c.1157A>C) in the general population?

ARAP3 p.His386Pro (c.1157A>C) is very rare (popmax 0.00536%, afr) (gnomAD).

What do computational predictors say about ARAP3 p.His386Pro (c.1157A>C)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

ARAP3 p.His386Pro

c.1157A>C · rs765300785 · VCV2383586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.63	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 1.9	GERP -1, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 8,347 bp · p 0.061 · regional, not allelic
Overall
CADD	16.75	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 0.00536% African / African-American · 4/74,682 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00118% 19/1,605,758 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,671
European (non-Finnish)	0.00128%	78,409

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.His386Pro
Coding: c.1157A>C
MANE Select: NM_022481
dbSNP: rs765300785
Type: single nucleotide variant
Location: chr5:141672862 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB

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-his386pro (accessed [today's date]).

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