Is RANGRF p.Asp27= (c.81C>T) pathogenic?

RANGRF p.Asp27= (c.81C>T) is classified Benign in RANGRF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.64%, eas); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Asp27= (c.81C>T)?

RANGRF p.Asp27= (c.81C>T) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Asp27= (c.81C>T) in the general population?

RANGRF p.Asp27= (c.81C>T) is low-frequency (popmax 1.64%, eas) (gnomAD).

RANGRF p.Asp27=

c.81C>T · rs3809740 · VCV241109

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, eas)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1	GERP 0.58, phastCons 1
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.64% East Asian · 735/44,874 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5%

Overall 0.255% 4,111/1,614,174 alleles · low-frequency exomes 3,585/1,461,826 · genomes 526/152,348 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.67%	37
East Asiangrpmax	1.64%	61
Ashkenazi Jewishnot grpmax-eligible	0.429%	233
Remaining individualsnot grpmax-eligible	0.256%	391
South Asian	0.217%	460
European (non-Finnish)	0.0986%	1,014
Middle Eastern	0.0495%	2,021
African / African-American	0.0133%	7,506
Admixed American	0.00833%	12,006

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp27=
Coding: c.81C>T
MANE Select: NM_016492
dbSNP: rs3809740
Type: single nucleotide variant
Location: chr17:8288959 (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-asp27 (accessed [today's date]).

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