Is ARF3 p.Phe51Cys (c.152T>G) pathogenic?

ARF3 p.Phe51Cys (c.152T>G) is classified Uncertain significance in ARF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1.

How common is ARF3 p.Phe51Cys (c.152T>G) in the general population?

ARF3 p.Phe51Cys (c.152T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF3 p.Phe51Cys (c.152T>G)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

ARF3 p.Phe51Cys

c.152T>G · VCV3774874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -14.22	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 1,283 bp · p 1e-16 · regional, not allelic
Overall
CADD	28.5	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.Phe51Cys
Coding: c.152T>G
MANE Select: NM_001659
Type: single nucleotide variant
Location: chr12:48940104 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.23 · 2 PDB
Residue 51: a β-strand

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-phe51cys (accessed [today's date]).

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