Is RANGRF p.Glu83= (c.249G>A) pathogenic?

RANGRF p.Glu83= (c.249G>A) is classified Likely benign in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-20). Very rare (popmax 0.00133%, afr).

How common is RANGRF p.Glu83= (c.249G>A) in the general population?

RANGRF p.Glu83= (c.249G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

RANGRF p.Glu83=

c.249G>A · rs751751942 · VCV515655

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.21	GERP -5.1, phastCons 0.88
Overall
CADD	5.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,046 alleles · very rare exomes 5/1,461,840 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,924
European (non-Finnish)	0.000508%	196,675

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.Glu83=
Coding: c.249G>A
MANE Select: NM_016492
dbSNP: rs751751942
Type: single nucleotide variant
Location: chr17:8289312 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 83: a β-strand; 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); a UniProt-annotated variant site (found in patients with 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

Similar variants

RANGRF p.Glu83Gly Uncertain significance ★ ⚠ same residue
RANGRF p.Glu83Lys Uncertain significance ★ ⚠ same residue
RANGRF c.77+5G>A Uncertain significance ★★ same type
RANGRF p.Ala56Val Uncertain significance ★★ ⚠ same type
RANGRF p.Arg130Lys Uncertain significance ★★ ⚠ same type
RANGRF p.Asp179Asn Uncertain significance ★★ ⚠ same type
RANGRF p.His81Arg Uncertain significance ★★ ⚠ same type
RANGRF p.Pro162Ser 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/rangrf-p-glu83 (accessed [today's date]).

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