Is RIGI p.Ala537= (c.1611C>T) pathogenic?

RIGI p.Ala537= (c.1611C>T) is classified Benign/Likely benign in RIGI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.2%, afr).

How common is RIGI p.Ala537= (c.1611C>T) in the general population?

RIGI p.Ala537= (c.1611C>T) is low-frequency (popmax 1.2%, afr) (gnomAD).

RIGI p.Ala537=

c.1611C>T · rs150568623 · VCV730407

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, afr)

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 -12	GERP -4.5
Overall
CADD	0.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.2% African / African-American · 902/74,886 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0642% 1,036/1,613,524 alleles · low-frequency exomes 476/1,461,472 · genomes 560/152,052 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.2%	83
Remaining individualsnot grpmax-eligible	0.08%	1,249
Admixed American	0.0751%	1,331
Middle Eastern	0.0165%	6,052
European (non-Finnish)	0.00314%	31,889
South Asian	0.0011%	90,972

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.Ala537=
Coding: c.1611C>T
MANE Select: NM_014314
dbSNP: rs150568623
Type: single nucleotide variant
Location: chr9:32481367 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 537: an α-helix; the 'interaction with zc3hav1' region

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

Similar variants

RIGI p.Ala537Ser Uncertain significance ★★ ⚠ same residue
RIGI p.Ala537Thr 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.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-ala537 (accessed [today's date]).

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