Is RANBP2 p.Ala684fs (c.2048_2049dup) pathogenic?

RANBP2 p.Ala684fs (c.20482049dup) is classified Uncertain significance in RANBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). No gnomAD frequency available for this variant.

How common is RANBP2 p.Ala684fs (c.2048_2049dup) in the general population?

RANBP2 p.Ala684fs (c.2048_2049dup) is no gnomAD frequency available for this variant (gnomAD).

RANBP2 p.Ala684fs

c.2048_2049dup · rs2467526074 · VCV2497891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RANBP2
Protein: p.Ala684fs
Coding: c.2048_2049dup
MANE Select: NM_006267
dbSNP: rs2467526074
Type: Duplication
Location: chr2:108753555 (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

SH3RF3 p.Asn684Asp Uncertain significance ★ ⚠ same residue
RANBP2 p.Arg563fs Uncertain significance ★★ same type
RANBP2 c.1063+8dup Likely benign ★★ same type
RANBP2 c.2383-3dup Benign/Likely benign ★★ same type
RANBP2 c.2467-11dup Benign/Likely benign ★★ same type
RANBP2 p.Arg412_Glu413insArg Uncertain significance ★ same type
RANBP2 p.Asp1965fs Uncertain significance ★ same type
RANBP2 p.Glu1659Ter 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-ala684fs (accessed [today's date]).

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