Is ARF5 p.Arg151Cys (c.451C>T) pathogenic?

ARF5 p.Arg151Cys (c.451C>T) is classified Uncertain significance in ARF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.7508); Very rare (popmax 0.00223%, eas).

How common is ARF5 p.Arg151Cys (c.451C>T) in the general population?

ARF5 p.Arg151Cys (c.451C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARF5 p.Arg151Cys (c.451C>T)?

AlphaMissense predicts likely pathogenic (score 0.7508) — an in-silico prediction, not a clinical call.

ARF5 p.Arg151Cys

c.451C>T · VCV4836426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7508	likely pathogenic
REVEL	0.709	pathogenic-leaning
SaProt	LLR -13.73	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 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,780 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	27.4	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 0.00223% East Asian · 1/44,878 alleles

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

Overall 0.000274% 4/1,461,650 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0011%	91,068
European (non-Finnish)	0.000169%	589,977

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: ARF5
Protein: p.Arg151Cys
Coding: c.451C>T
MANE Select: NM_001662
Type: single nucleotide variant
Location: chr7:127591083 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 1 PDB

Full ARF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARF5 p.Thr164= Benign ★★ same type
ARF5 p.Arg149Cys Uncertain significance ★ ⚠ same type
ARF5 p.Arg180Cys Uncertain significance ★ ⚠ same type
ARF5 p.Arg97Trp Uncertain significance ★ ⚠ same type
ARF5 p.Asp114Asn Uncertain significance ★ ⚠ same type
ARF5 p.Gln112Ter Uncertain significance ★ same type
ARF5 p.Glu138Gln Uncertain significance ★ ⚠ same type
ARF5 p.Gly70Cys 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/arf5-p-arg151cys (accessed [today's date]).

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