Is RANGRF p.Asp179Tyr (c.535G>T) pathogenic?

RANGRF p.Asp179Tyr (c.535G>T) is classified Uncertain significance in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-05). AlphaMissense: ambiguous (0.3427); Absent from gnomAD v4.1; Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Asp179Tyr (c.535G>T)?

RANGRF p.Asp179Tyr (c.535G>T) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Asp179Tyr (c.535G>T) in the general population?

RANGRF p.Asp179Tyr (c.535G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RANGRF p.Asp179Tyr (c.535G>T)?

AlphaMissense predicts ambiguous (score 0.3427) — an in-silico prediction, not a clinical call.

RANGRF p.Asp179Tyr

c.535G>T · rs374174477 · VCV846279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3427 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

cardiac rhythm disease

Computational evidence

Protein change
AlphaMissense	0.3427	ambiguous
REVEL	0.73	pathogenic-leaning
SaProt	LLR -7.06	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,144 bp · p 0.49 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RANGRF
Protein: p.Asp179Tyr
Coding: c.535G>T
MANE Select: NM_016492
dbSNP: rs374174477
Type: single nucleotide variant
Location: chr17:8289910 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 179: 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.Asp179Asn 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.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-asp179tyr (accessed [today's date]).

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