Is RIGI p.Ser144Pro (c.430T>C) pathogenic?

RIGI p.Ser144Pro (c.430T>C) is classified Uncertain significance in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.5049); Absent from gnomAD v4.1.

How common is RIGI p.Ser144Pro (c.430T>C) in the general population?

RIGI p.Ser144Pro (c.430T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RIGI p.Ser144Pro (c.430T>C)?

AlphaMissense predicts ambiguous (score 0.5049) — an in-silico prediction, not a clinical call.

RIGI p.Ser144Pro

c.430T>C · rs2489339104 · VCV2987958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5049 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5049	ambiguous
REVEL	0.06	moderately benign-leaning
SaProt	LLR -13.39	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -4.3, phastCons 0.21
Regional constraint	o/e 1.04	unconstrained · MANE · 37 kb · p 0.5 · regional, not allelic
Overall
CADD	10.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RIGI
Protein: p.Ser144Pro
Coding: c.430T>C
MANE Select: NM_014314
dbSNP: rs2489339104
Type: single nucleotide variant
Location: chr9:32492532 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 144: the card 2 domain; an α-helix

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

Similar variants

RIGI p.Ser144Phe Benign/Likely benign ★★ 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
RIGI p.Ala774Thr 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-ser144pro (accessed [today's date]).

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