Is RIGI p.Pro676= (c.2028G>A) pathogenic?

RIGI p.Pro676= (c.2028G>A) is classified Likely benign in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). Very rare (popmax 0.00683%, amr).

How common is RIGI p.Pro676= (c.2028G>A) in the general population?

RIGI p.Pro676= (c.2028G>A) is very rare (popmax 0.00683%, amr) (gnomAD).

RIGI p.Pro676=

c.2028G>A · rs772210224 · VCV3021566

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00683%, amr)

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 -2	GERP -4.3
Overall
CADD	4.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00683% Admixed American · 4/58,576 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000816% 13/1,592,206 alleles · very rare exomes 13/1,439,886 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00683%	14,644
Ashkenazi Jewishnot grpmax-eligible	0.00346%	28,902
South Asian	0.00112%	89,194
European (non-Finnish)	0.000601%	166,354

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.Pro676=
Coding: c.2028G>A
MANE Select: NM_014314
dbSNP: rs772210224
Type: single nucleotide variant
Location: chr9:32467919 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 676: an α-helix; the helicase c-terminal domain; the 'interaction with zc3hav1' region

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

Similar variants

RIGI p.Pro676Gln Uncertain significance ★ ⚠ same residue
RIGI p.Pro676Leu 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-pro676 (accessed [today's date]).

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