Is ARF3 p.Arg19Cys (c.55C>T) pathogenic?

ARF3 p.Arg19Cys (c.55C>T) is classified Pathogenic in ARF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely pathogenic (0.9959); Absent from gnomAD v4.1.

How common is ARF3 p.Arg19Cys (c.55C>T) in the general population?

ARF3 p.Arg19Cys (c.55C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF3 p.Arg19Cys (c.55C>T)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

ARF3 p.Arg19Cys

c.55C>T · VCV3378073

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,756)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic ✓ concordant with ClinVar
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -14.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.16	constrained · MANE · 1,283 bp · p 1e-16 · regional, not allelic
Overall
CADD	29.0	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

No allele count reported in gnomAD v4.1 (AN 1,613,756). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARF3
Protein: p.Arg19Cys
Coding: c.55C>T
MANE Select: NM_001659
Type: single nucleotide variant
Location: chr12:48941041 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.23 · 2 PDB
Residue 19: a β-strand

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

Similar variants

ARF3 p.Arg19His Uncertain significance ★ ⚠ same residue
ARF3 p.Asp93Asn Pathogenic/Likely pathogenic ★★ same type
ARF3 p.His80= Benign ★★ 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-arg19cys (accessed [today's date]).

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