Is RANBP2 p.Pro985Arg (c.2954C>G) pathogenic?

RANBP2 p.Pro985Arg (c.2954C>G) is classified Uncertain significance in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-25). AlphaMissense: likely benign (0.209); Absent from gnomAD v4.1.

How common is RANBP2 p.Pro985Arg (c.2954C>G) in the general population?

RANBP2 p.Pro985Arg (c.2954C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RANBP2 p.Pro985Arg (c.2954C>G)?

AlphaMissense predicts likely benign (score 0.209) — an in-silico prediction, not a clinical call.

RANBP2 p.Pro985Arg

c.2954C>G · rs368547122 · VCV1698176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.209 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.209	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,957 bp · p 0.18 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: RANBP2
Protein: p.Pro985Arg
Coding: c.2954C>G
MANE Select: NM_006267
dbSNP: rs368547122
Type: single nucleotide variant
Location: chr2:108763493 (GRCh38)
Gene constraint: LOEUF 0.231 · pLI 1.00 (gnomAD)

Full RANBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RANBP2 p.Pro985= Benign ★★ same residue
RANBP2 p.Pro985Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EDAR p.Arg358Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
RANBP2 p.Thr585Met Pathogenic/Likely pathogenic ★★ ⚠ same type
EDAR p.Leu353Phe Uncertain significance ★★ ⚠ same type
RANBP2 c.406-2A>G Uncertain significance ★★ same type
RANBP2 p.Ala2337Val Uncertain significance ★★ same type
RANBP2 p.Ala2564Ser 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/ranbp2-p-pro985arg (accessed [today's date]).

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