Is RANGRF p.Val80Ile (c.238G>A) pathogenic?

RANGRF p.Val80Ile (c.238G>A) is classified Uncertain significance in RANGRF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). AlphaMissense: likely benign (0.0742); Very rare (popmax 0.00237%, nfe); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Val80Ile (c.238G>A)?

RANGRF p.Val80Ile (c.238G>A) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Val80Ile (c.238G>A) in the general population?

RANGRF p.Val80Ile (c.238G>A) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about RANGRF p.Val80Ile (c.238G>A)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

RANGRF p.Val80Ile

c.238G>A · rs1990291243 · VCV2715610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiac rhythm disease

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.44	GERP -5.1, phastCons 0.018
Regional constraint	o/e 0.96	unconstrained · MANE · 1,144 bp · p 0.49 · regional, not allelic
Overall
CADD	11.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,024 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,614,068 alleles · very rare exomes 29/1,461,796 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Val80Ile
Coding: c.238G>A
MANE Select: NM_016492
dbSNP: rs1990291243
Type: single nucleotide variant
Location: chr17:8289301 (GRCh38)

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

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-val80ile (accessed [today's date]).

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