Is RIGI p.Pro50Gln (c.149C>A) pathogenic?

RIGI p.Pro50Gln (c.149C>A) is classified Conflicting classifications of pathogenicity in RIGI (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-15). AlphaMissense: likely benign (0.1548); Ultra-rare (popmax 0.0461%, sas); Associated with Inborn genetic diseases.

What condition is associated with RIGI p.Pro50Gln (c.149C>A)?

RIGI p.Pro50Gln (c.149C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RIGI p.Pro50Gln (c.149C>A) in the general population?

RIGI p.Pro50Gln (c.149C>A) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

What do computational predictors say about RIGI p.Pro50Gln (c.149C>A)?

AlphaMissense predicts likely benign (score 0.1548) — an in-silico prediction, not a clinical call.

RIGI p.Pro50Gln

c.149C>A · rs533959324 · VCV1490091

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1548	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.16	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 4.2	GERP 0.55, phastCons 0.74
Regional constraint	o/e 1.04	unconstrained · MANE · 37 kb · p 0.5 · regional, not allelic
Overall
CADD	16.93	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 0.0461% South Asian · 42/91,072 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00285% 46/1,614,086 alleles · ultra-rare exomes 39/1,461,854 · genomes 7/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,168
Remaining individualsnot grpmax-eligible	0.0032%	31,250
African / African-American	0.00133%	75,028
European (non-Finnish)	8.47e-05%	1,180,013

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.Pro50Gln
Coding: c.149C>A
MANE Select: NM_014314
dbSNP: rs533959324
Type: single nucleotide variant
Location: chr9:32500897 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 50: the card 1 domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIGI p.Pro50Ala Uncertain significance ★ ⚠ same residue
RIGI p.Ala436Val Uncertain significance ★★ ⚠ same condition
RIGI p.Ala537Ser Uncertain significance ★★ ⚠ same condition
RIGI p.Ala537Thr Uncertain significance ★★ ⚠ same condition
RIGI p.Ala774Thr Uncertain significance ★★ ⚠ same condition
RIGI p.Arg109Cys Uncertain significance ★★ ⚠ same condition
RIGI p.Arg34Gly Uncertain significance ★★ ⚠ same condition
RIGI p.Arg664His 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/rigi-p-pro50gln (accessed [today's date]).

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