Is ARF3 p.Arg149Ser (c.445C>A) pathogenic?

ARF3 p.Arg149Ser (c.445C>A) is classified Uncertain significance in ARF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-10). AlphaMissense: likely pathogenic (0.9583); Absent from gnomAD v4.1.

How common is ARF3 p.Arg149Ser (c.445C>A) in the general population?

ARF3 p.Arg149Ser (c.445C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF3 p.Arg149Ser (c.445C>A)?

AlphaMissense predicts likely pathogenic (score 0.9583) — an in-silico prediction, not a clinical call.

ARF3 p.Arg149Ser

c.445C>A · VCV3360894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9583	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -13.53	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 814 bp · p 5.9e-10 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARF3
Protein: p.Arg149Ser
Coding: c.445C>A
MANE Select: NM_001659
Type: single nucleotide variant
Location: chr12:48939048 (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-arg149ser (accessed [today's date]).

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