Is ARF5 p.Arg97Trp (c.289C>T) pathogenic?

ARF5 p.Arg97Trp (c.289C>T) is classified Uncertain significance in ARF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.6273); Very rare (popmax 0.00401%, afr).

How common is ARF5 p.Arg97Trp (c.289C>T) in the general population?

ARF5 p.Arg97Trp (c.289C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ARF5 p.Arg97Trp (c.289C>T)?

AlphaMissense predicts likely pathogenic (score 0.6273) — an in-silico prediction, not a clinical call.

ARF5 p.Arg97Trp

c.289C>T · VCV4130880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6273	likely pathogenic
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -15.63	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 3.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,780 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	29.5	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

Grpmax group 0.00401% African / African-American · 3/74,862 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00242% 39/1,613,798 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,954
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)	0.00271%	36,873
Admixed American	0.00167%	59,996
Finnishnot grpmax-eligible	0.00156%	64,004

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.Arg97Trp
Coding: c.289C>T
MANE Select: NM_001662
Type: single nucleotide variant
Location: chr7:127590096 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 1 PDB
Residue 97: an α-helix

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.Arg151Cys Uncertain significance ★ ⚠ same type
ARF5 p.Arg180Cys 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-arg97trp (accessed [today's date]).

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