Is RIGI p.Pro848= (c.2544C>T) pathogenic?

RIGI p.Pro848= (c.2544C>T) is classified Likely benign in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). Very rare (popmax 0.00223%, eas).

How common is RIGI p.Pro848= (c.2544C>T) in the general population?

RIGI p.Pro848= (c.2544C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

RIGI p.Pro848=

c.2544C>T · rs1479193304 · VCV1666019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -3, phastCons 0.49
Overall
CADD	3.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 0.000124% 2/1,613,960 alleles · very rare exomes 2/1,461,866 · genomes 0/152,094 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0011%	91,068

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.Pro848=
Coding: c.2544C>T
MANE Select: NM_014314
dbSNP: rs1479193304
Type: single nucleotide variant
Location: chr9:32457356 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 848: the rlr ctr domain; the 'interaction with zc3hav1' region; the 'mediates interaction with rnf135' region

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

Similar variants

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
RIGI p.Ala537Thr Uncertain significance ★★ ⚠ same type
RIGI p.Ala774Thr Uncertain significance ★★ ⚠ same type
RIGI p.Arg109Cys 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-pro848 (accessed [today's date]).

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