Is RIGI p.Pro403Ser (c.1207C>T) pathogenic?

RIGI p.Pro403Ser (c.1207C>T) is classified Likely benign in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). AlphaMissense: likely pathogenic (0.9208); Very rare (popmax 0.00667%, afr).

How common is RIGI p.Pro403Ser (c.1207C>T) in the general population?

RIGI p.Pro403Ser (c.1207C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about RIGI p.Pro403Ser (c.1207C>T)?

AlphaMissense predicts likely pathogenic (score 0.9208) — an in-silico prediction, not a clinical call.

RIGI p.Pro403Ser

c.1207C>T · VCV4902869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9208	likely pathogenic · top 6% in RIGI
REVEL	0.454	indeterminate
SaProt	LLR -10.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,762 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	25.0	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 0.00667% African / African-American · 5/75,014 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,613,866 alleles · very rare exomes 1/1,461,582 · genomes 5/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	15,003
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Pro403Ser
Coding: c.1207C>T
MANE Select: NM_014314
Type: single nucleotide variant
Location: chr9:32487950 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 403: an α-helix; the helicase atp-binding 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-pro403ser (accessed [today's date]).

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