Is RANGRF p.Asp6fs (c.16_17del) pathogenic?

RANGRF p.Asp6fs (c.1617del) is classified Uncertain significance in RANGRF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-01). Very rare (popmax 0.000932%, nfe); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Asp6fs (c.16_17del)?

RANGRF p.Asp6fs (c.16_17del) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Asp6fs (c.16_17del) in the general population?

RANGRF p.Asp6fs (c.16_17del) is very rare (popmax 0.000932%, nfe) (gnomAD).

RANGRF p.Asp6fs

c.16_17del · rs752068609 · VCV1677880

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

cardiac rhythm disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -0.55, phastCons 0.93
Overall
CADD	18.49	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,048 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,996 alleles · very rare exomes 10/1,461,772 · genomes 1/152,224 · 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.Asp6fs
Coding: c.16_17del
MANE Select: NM_016492
dbSNP: rs752068609
Type: Microsatellite
Location: chr17:8288800 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 6: a β-strand

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-asp6fs (accessed [today's date]).

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