Is RANGRF p.Thr176= (c.528C>G) pathogenic?

RANGRF p.Thr176= (c.528C>G) is classified Likely benign in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-06). Very rare (popmax 0.00801%, afr).

How common is RANGRF p.Thr176= (c.528C>G) in the general population?

RANGRF p.Thr176= (c.528C>G) is very rare (popmax 0.00801%, afr) (gnomAD).

RANGRF p.Thr176=

c.528C>G · rs371169825 · VCV508788

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.203	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.26	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.033	GERP -4.8, phastCons 0.76
Overall
CADD	6.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,910 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,614,030 alleles · very rare exomes 0/1,461,870 · genomes 6/152,160 · joint denominator

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.Thr176=
Coding: c.528C>G
MANE Select: NM_016492
dbSNP: rs371169825
Type: single nucleotide variant
Location: chr17:8289903 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 176: 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

Similar variants

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
RANGRF p.Ser84Ala Uncertain significance ★★ ⚠ same type
RANGRF p.Val122Met 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-thr176 (accessed [today's date]).

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