Is RIGI p.His623= (c.1869C>T) pathogenic?

RIGI p.His623= (c.1869C>T) is classified Likely benign in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Very rare (popmax 0.00891%, eas).

How common is RIGI p.His623= (c.1869C>T) in the general population?

RIGI p.His623= (c.1869C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

RIGI p.His623=

c.1869C>T · rs549735258 · VCV1462036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 1.2	GERP -0.037, phastCons 0.72
Overall
CADD	5.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00105% 17/1,614,188 alleles · very rare exomes 15/1,461,840 · genomes 2/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
South Asian	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0064%	15,626
African / African-American	0.00133%	75,068

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.His623=
Coding: c.1869C>T
MANE Select: NM_014314
dbSNP: rs549735258
Type: single nucleotide variant
Location: chr9:32477037 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 623: 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-his623 (accessed [today's date]).

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