Is RIGI p.Arg480Ser (c.1440G>C) pathogenic?

RIGI p.Arg480Ser (c.1440G>C) is classified Uncertain significance in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1554); Very rare (popmax 0.000678%, nfe).

How common is RIGI p.Arg480Ser (c.1440G>C) in the general population?

RIGI p.Arg480Ser (c.1440G>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about RIGI p.Arg480Ser (c.1440G>C)?

AlphaMissense predicts likely benign (score 0.1554) — an in-silico prediction, not a clinical call.

RIGI p.Arg480Ser

c.1440G>C · rs528176202 · VCV1358025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1554 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1554	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -4.2
Regional constraint	o/e 1.10	unconstrained · MANE · 2,408 bp · p 0.37 · regional, not allelic
Overall
CADD	1.713	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 0.000678% European (non-Finnish) · 8/1,179,348 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,609,776 alleles · very rare exomes 6/1,457,748 · genomes 2/152,028 · 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: RIGI
Protein: p.Arg480Ser
Coding: c.1440G>C
MANE Select: NM_014314
dbSNP: rs528176202
Type: single nucleotide variant
Location: chr9:32485215 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 480: an α-helix; the 'interaction with zc3hav1' region

Full RIGI gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIGI p.Arg480Gly Uncertain significance ★ ⚠ same residue
RIGI p.Arg480Lys Uncertain significance ★ ⚠ same residue
RIGI p.Arg480= Benign ★ same residue
RIGI c.1923+1G>A Uncertain significance ★★ same type
RIGI c.954-6T>G Uncertain significance ★★ same type
RIGI p.Ala436Val Uncertain significance ★★ ⚠ same type
RIGI p.Ala486Thr Uncertain significance ★★ ⚠ same type
RIGI p.Ala537Ser Uncertain significance ★★ ⚠ same type

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/rigi-p-arg480ser (accessed [today's date]).

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