Is RIGI p.Pro885Ser (c.2653C>T) pathogenic?

RIGI p.Pro885Ser (c.2653C>T) is classified Likely benign in RIGI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-17). AlphaMissense: likely pathogenic (0.5651); Rare (popmax 0.114%, nfe).

How common is RIGI p.Pro885Ser (c.2653C>T) in the general population?

RIGI p.Pro885Ser (c.2653C>T) is rare (popmax 0.114%, nfe) (gnomAD).

What do computational predictors say about RIGI p.Pro885Ser (c.2653C>T)?

AlphaMissense predicts likely pathogenic (score 0.5651) — an in-silico prediction, not a clinical call.

RIGI p.Pro885Ser

c.2653C>T · rs138425677 · VCV1017102

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.5651 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5651	likely pathogenic
REVEL	0.445	indeterminate
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,257 bp · p 0.84 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% European (non-Finnish) · 1,349/1,180,016 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0894% 1,443/1,614,070 alleles · rare exomes 1,368/1,461,874 · genomes 75/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.114%	875
Finnishnot grpmax-eligible	0.0406%	2,461
South Asian	0.0373%	2,679
Remaining individualsnot grpmax-eligible	0.0304%	3,290
African / African-American	0.0173%	5,770
Admixed American	0.00333%	30,004

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.Pro885Ser
Coding: c.2653C>T
MANE Select: NM_014314
dbSNP: rs138425677
Type: single nucleotide variant
Location: chr9:32457247 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 885: a β-strand; the rlr ctr domain; the 'interaction with zc3hav1' region; the 'mediates interaction with rnf135' 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-pro885ser (accessed [today's date]).

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