Is RIGI p.Asp641= (c.1923C>T) pathogenic?

RIGI p.Asp641= (c.1923C>T) is classified Uncertain significance in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-09). Ultra-rare (popmax 0.0562%, sas).

How common is RIGI p.Asp641= (c.1923C>T) in the general population?

RIGI p.Asp641= (c.1923C>T) is ultra-rare (popmax 0.0562%, sas) (gnomAD).

RIGI p.Asp641=

c.1923C>T · rs755898188 · VCV1402149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0562%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.4	GERP -3.5, phastCons 0.65
Overall
CADD	9.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0562% South Asian · 51/90,812 alleles

Filtering AF 0.0438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0395%

Overall 0.00509% 82/1,612,076 alleles · ultra-rare exomes 80/1,459,928 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0562%	1,781
Admixed American	0.00336%	29,790
European (non-Finnish)	0.00237%	42,112
Remaining individualsnot grpmax-eligible	0.0016%	62,392

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.Asp641=
Coding: c.1923C>T
MANE Select: NM_014314
dbSNP: rs755898188
Type: single nucleotide variant
Location: chr9:32476983 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 641: 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 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-asp641 (accessed [today's date]).

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