Is RAN p.Asn55= (c.165C>T) pathogenic?

RAN p.Asn55= (c.165C>T) is classified Benign in RAN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.208%, nfe).

How common is RAN p.Asn55= (c.165C>T) in the general population?

RAN p.Asn55= (c.165C>T) is rare (popmax 0.208%, nfe) (gnomAD).

RAN p.Asn55=

c.165C>T · rs145207608 · VCV713516

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.208%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	phastCons 1
Overall
CADD	13.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.208% European (non-Finnish) · 2,456/1,180,040 alleles

Filtering AF 0.201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.255% 4,111/1,614,224 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.27%	44
European (non-Finnish)grpmax	0.208%	480
Remaining individualsnot grpmax-eligible	0.198%	504
Admixed American	0.0416%	2,401
African / African-American	0.0386%	2,588
Middle Eastern	0.0165%	6,062
South Asian	0.0154%	6,507
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
East Asian	0.00223%	44,894

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RAN
Protein: p.Asn55=
Coding: c.165C>T
MANE Select: NM_006325
dbSNP: rs145207608
Type: single nucleotide variant
Location: chr12:130873046 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 139 PDB
Residue 55: the small gtpase ran-type domain; a β-strand

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

Similar variants

RAN p.Glu113Gly 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/ran-p-asn55 (accessed [today's date]).

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