Is ARF3 p.Pro47Ser (c.139C>T) pathogenic?

ARF3 p.Pro47Ser (c.139C>T) is classified Conflicting classifications of pathogenicity in ARF3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-05-27). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with Atrophy/Degeneration affecting the central nervous system.

How common is ARF3 p.Pro47Ser (c.139C>T) in the general population?

ARF3 p.Pro47Ser (c.139C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF3 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

ARF3 p.Pro47Ser

Q: What condition is associated with ARF3 p.Pro47Ser (c.139C>T)?

ARF3 p.Pro47Ser (c.139C>T) is associated with Atrophy/Degeneration affecting the central nervous system, intellectual disability (ClinVar).

c.139C>T · rs2498897350 · VCV1697210

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Atrophy/Degeneration affecting the central nervous system

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -12.14	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	28.0	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

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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_001659
dbSNP: rs2498897350
Type: single nucleotide variant
Location: chr12:48940957 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.23 · 2 PDB

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

Disease context

Atrophy/Degeneration affecting the central nervous system — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability

Similar variants

ARF3 p.Asp93Asn Pathogenic/Likely pathogenic ★★ same condition
ARF3 p.Asp67Val Pathogenic ★ same condition
ARF3 p.Leu12Val Likely pathogenic ★ ⚠ same condition
ARF3 p.Lys127Glu Pathogenic ★ same condition
ARF3 p.Thr32Asn Pathogenic ★ same condition
ARF3 p.His80= Benign ★★ same type
ARF3 p.Arg19Cys Pathogenic ★ same type
ARF3 p.Arg99Leu Likely 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-pro47ser (accessed [today's date]).

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