Is RIGI p.Ala30Val (c.89C>T) pathogenic?

RIGI p.Ala30Val (c.89C>T) is classified Conflicting classifications of pathogenicity in RIGI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-29). AlphaMissense: likely benign (0.0951); Ultra-rare (popmax 0.0867%, afr).

How common is RIGI p.Ala30Val (c.89C>T) in the general population?

RIGI p.Ala30Val (c.89C>T) is ultra-rare (popmax 0.0867%, afr) (gnomAD).

What do computational predictors say about RIGI p.Ala30Val (c.89C>T)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

RIGI p.Ala30Val

c.89C>T · rs147964586 · VCV3004439

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP 0.14, phastCons 0.004
Regional constraint	o/e 1.04	unconstrained · MANE · 37 kb · p 0.5 · regional, not allelic
Overall
CADD	19.68	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 0.0867% African / African-American · 65/74,998 alleles

Filtering AF 0.0698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0636%

Overall 0.00713% 115/1,613,660 alleles · ultra-rare exomes 80/1,461,438 · genomes 35/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0867%	1,154
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Middle Eastern	0.033%	3,030
East Asian	0.00223%	44,860
South Asian	0.0022%	45,534
European (non-Finnish)	0.00119%	84,261

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.Ala30Val
Coding: c.89C>T
MANE Select: NM_014314
dbSNP: rs147964586
Type: single nucleotide variant
Location: chr9:32526078 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 30: the card 1 domain; a turn

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

Similar variants

RIGI p.Ala30Thr Likely benign ★ same residue
RIGI p.Ala30Ile Uncertain significance ★ 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
RIGI p.Ala537Thr 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-ala30val (accessed [today's date]).

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