Is RANGRF p.Arg59= (c.177G>A) pathogenic?

RANGRF p.Arg59= (c.177G>A) is classified Likely benign in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). Very rare (popmax 0.00133%, afr); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Arg59= (c.177G>A)?

RANGRF p.Arg59= (c.177G>A) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Arg59= (c.177G>A) in the general population?

RANGRF p.Arg59= (c.177G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

RANGRF p.Arg59=

c.177G>A · rs758596981 · VCV2993121

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

cardiac rhythm disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.5	GERP -4.7
Overall
CADD	4.098	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Overall 0.000124% 2/1,613,672 alleles · very rare exomes 1/1,461,432 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
European (non-Finnish)	8.47e-05%	1,179,988

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: RANGRF
Protein: p.Arg59=
Coding: c.177G>A
MANE Select: NM_016492
dbSNP: rs758596981
Type: single nucleotide variant
Location: chr17:8289055 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 59: the 'interaction with ran' region

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

Disease context

cardiac rhythm disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RANGRF p.Arg59Gly Uncertain significance ★ ⚠ same residue
RANGRF p.Arg59Leu Uncertain significance ★ ⚠ same residue
RANGRF p.Arg59Pro Uncertain significance ★ ⚠ same residue
RANGRF p.Arg59Trp Uncertain significance ★ ⚠ same residue
RANGRF c.77+5G>A Uncertain significance ★★ same condition
RANGRF p.Ala56Val Uncertain significance ★★ ⚠ same condition
RANGRF p.Arg130Lys Uncertain significance ★★ ⚠ same condition
RANGRF p.Asp179Asn Uncertain significance ★★ ⚠ same condition

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/rangrf-p-arg59 (accessed [today's date]).

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