Is RIGI p.Ile300= (c.900C>T) pathogenic?

RIGI p.Ile300= (c.900C>T) is classified Likely benign in RIGI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). Very rare (popmax 0.000424%, nfe).

How common is RIGI p.Ile300= (c.900C>T) in the general population?

RIGI p.Ile300= (c.900C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

RIGI p.Ile300=

c.900C>T · rs1327513513 · VCV1934993

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 0.89	GERP -4.3, phastCons 1
Overall
CADD	7.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,504 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,078 alleles · very rare exomes 2/1,460,964 · genomes 3/152,114 · 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.Ile300=
Coding: c.900C>T
MANE Select: NM_014314
dbSNP: rs1327513513
Type: single nucleotide variant
Location: chr9:32488787 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 300: the helicase atp-binding domain; the 'interaction with zc3hav1' region; an α-helix

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-ile300 (accessed [today's date]).

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