Is RANGRF p.Val42Leu (c.124G>T) pathogenic?

RANGRF p.Val42Leu (c.124G>T) is classified Likely benign in RANGRF (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0997); Rare (popmax 0.227%, sas); Associated with cardiac rhythm disease.

What condition is associated with RANGRF p.Val42Leu (c.124G>T)?

RANGRF p.Val42Leu (c.124G>T) is associated with cardiac rhythm disease (ClinVar).

How common is RANGRF p.Val42Leu (c.124G>T) in the general population?

RANGRF p.Val42Leu (c.124G>T) is rare (popmax 0.227%, sas) (gnomAD).

What do computational predictors say about RANGRF p.Val42Leu (c.124G>T)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

RANGRF p.Val42Leu

c.124G>T · rs548428743 · VCV1110143

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, sas)

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	0.0997	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -0.66, phastCons 0.001
Regional constraint	o/e 0.96	unconstrained · MANE · 1,144 bp · p 0.49 · regional, not allelic
Overall
CADD	14.41	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

Grpmax group 0.227% South Asian · 207/91,088 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.0136% 220/1,614,122 alleles · rare exomes 208/1,461,776 · genomes 12/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.227%	440
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.000593%	168,577

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.Val42Leu
Coding: c.124G>T
MANE Select: NM_016492
dbSNP: rs548428743
Type: single nucleotide variant
Location: chr17:8289002 (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-val42leu (accessed [today's date]).

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