Is RANGRF p.Ala62= (c.186G>T) pathogenic?

RANGRF p.Ala62= (c.186G>T) is classified Likely benign in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-30). Very rare (popmax 0.00667%, afr); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Ala62= (c.186G>T)?

RANGRF p.Ala62= (c.186G>T) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Ala62= (c.186G>T) in the general population?

RANGRF p.Ala62= (c.186G>T) is very rare (popmax 0.00667%, afr) (gnomAD).

RANGRF p.Ala62=

c.186G>T · rs1053514842 · VCV1585384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.25	GERP -0.66, phastCons 0.004
Overall
CADD	7.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,944 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000496% 8/1,613,496 alleles · very rare exomes 4/1,461,246 · genomes 4/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,989
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000169%	589,977

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.Ala62=
Coding: c.186G>T
MANE Select: NM_016492
dbSNP: rs1053514842
Type: single nucleotide variant
Location: chr17:8289064 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 62: the 'interaction with ran' region; an α-helix; a UniProt-annotated variant site (found in patients with cardiac arrhythmias including brugada syndrome; uncertain significance; loss of function in enhancing the expression of scn5a at the cell membrane)

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.Ala62Gly 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
RANGRF p.His81Arg Uncertain significance ★★ ⚠ same condition
RANGRF p.Pro162Ser Uncertain significance ★★ ⚠ same condition
RANGRF p.Ser84Ala 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-ala62 (accessed [today's date]).

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