Is ARF5 p.Arg149Cys (c.445C>T) pathogenic?

ARF5 p.Arg149Cys (c.445C>T) is classified Uncertain significance in ARF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: ambiguous (0.3657); Very rare (popmax 0.00449%, nfe).

How common is ARF5 p.Arg149Cys (c.445C>T) in the general population?

ARF5 p.Arg149Cys (c.445C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about ARF5 p.Arg149Cys (c.445C>T)?

AlphaMissense predicts ambiguous (score 0.3657) — an in-silico prediction, not a clinical call.

ARF5 p.Arg149Cys

c.445C>T · rs751785636 · VCV3128327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3657	ambiguous
REVEL	0.661	pathogenic-leaning
SaProt	LLR -14.25	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,780 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00449% European (non-Finnish) · 53/1,179,988 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00359% 58/1,613,900 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,264
Admixed American	0.00334%	29,968
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	74,938
South Asian	0.0011%	91,068

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.Arg149Cys
Coding: c.445C>T
MANE Select: NM_001662
dbSNP: rs751785636
Type: single nucleotide variant
Location: chr7:127591077 (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.Arg151Cys 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-arg149cys (accessed [today's date]).

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