Is ARF3 p.Arg151His (c.452G>A) pathogenic?

ARF3 p.Arg151His (c.452G>A) is classified Uncertain significance in ARF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely pathogenic (0.703); Very rare (popmax 0.000169%, nfe).

How common is ARF3 p.Arg151His (c.452G>A) in the general population?

ARF3 p.Arg151His (c.452G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ARF3 p.Arg151His (c.452G>A)?

AlphaMissense predicts likely pathogenic (score 0.703) — an in-silico prediction, not a clinical call.

ARF3 p.Arg151His

c.452G>A · rs1940205418 · VCV2579832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.703	likely pathogenic
REVEL	0.398	indeterminate
SaProt	LLR -12.52	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 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 814 bp · p 5.9e-10 · regional, not allelic
Overall
CADD	32.0	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 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,674 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: ARF3
Protein: p.Arg151His
Coding: c.452G>A
MANE Select: NM_001659
dbSNP: rs1940205418
Type: single nucleotide variant
Location: chr12:48939041 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.23 · 2 PDB

Full ARF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARF3 p.Asp93Asn Pathogenic/Likely pathogenic ★★ same type
ARF3 p.His80= Benign ★★ same type
ARF3 p.Arg19Cys Pathogenic ★ same type
ARF3 p.Arg99Leu Likely pathogenic ★ same type
ARF3 p.Asn126Asp Likely pathogenic ★ same type
ARF3 p.Asn60Ile Likely pathogenic ★ same type
ARF3 p.Asp67Ala Likely pathogenic ★ same type
ARF3 p.Asp67Val Pathogenic ★ 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/arf3-p-arg151his (accessed [today's date]).

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