Is RANGRF p.Gln170= (c.510G>A) pathogenic?

RANGRF p.Gln170= (c.510G>A) is classified Benign in RANGRF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.258%, nfe); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Gln170= (c.510G>A)?

RANGRF p.Gln170= (c.510G>A) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Gln170= (c.510G>A) in the general population?

RANGRF p.Gln170= (c.510G>A) is rare (popmax 0.258%, nfe) (gnomAD).

RANGRF p.Gln170=

c.510G>A · rs35420920 · VCV138889

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, nfe)

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 1.5	GERP -2, phastCons 1
Overall
CADD	4.963	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% European (non-Finnish) · 3,048/1,180,040 alleles

Filtering AF 0.251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.247%

Overall 0.223% 3,592/1,614,180 alleles · rare exomes 3,251/1,461,880 · genomes 341/152,300 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.479%	209
European (non-Finnish)grpmax	0.258%	387
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
Remaining individualsnot grpmax-eligible	0.158%	631
South Asian	0.0549%	1,822
Admixed American	0.0283%	3,531
African / African-American	0.028%	3,573

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: RANGRF
Protein: p.Gln170=
Coding: c.510G>A
MANE Select: NM_016492
dbSNP: rs35420920
Type: single nucleotide variant
Location: chr17:8289885 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 170: 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 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
RANGRF p.Val122Met 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-gln170 (accessed [today's date]).

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