Is RIGI p.Arg71His (c.212G>A) pathogenic?

RIGI p.Arg71His (c.212G>A) is classified Benign/Likely benign in RIGI (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1563); Low-frequency (popmax 1.87%, nfe).

How common is RIGI p.Arg71His (c.212G>A) in the general population?

RIGI p.Arg71His (c.212G>A) is low-frequency (popmax 1.87%, nfe) (gnomAD).

What do computational predictors say about RIGI p.Arg71His (c.212G>A)?

AlphaMissense predicts likely benign (score 0.1563) — an in-silico prediction, not a clinical call.

RIGI p.Arg71His

c.212G>A · rs72710678 · VCV774885

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1563 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1563	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP -0.44, phastCons 0.56
Regional constraint	o/e 1.04	unconstrained · MANE · 37 kb · p 0.5 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 1.87% European (non-Finnish) · 22,121/1,179,960 alleles

Filtering AF 1.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.85%

Overall 1.55% 24,938/1,614,066 alleles · low-frequency exomes 23,459/1,461,820 · genomes 1,479/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.87%	53
Remaining individualsnot grpmax-eligible	1.52%	66
South Asian	0.94%	106
Admixed American	0.723%	138
Middle Eastern	0.544%	184
Ashkenazi Jewishnot grpmax-eligible	0.524%	191
Finnishnot grpmax-eligible	0.3%	333
African / African-American	0.26%	385
East Asian	0.00223%	44,872

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.Arg71His
Coding: c.212G>A
MANE Select: NM_014314
dbSNP: rs72710678
Type: single nucleotide variant
Location: chr9:32500834 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 71: the card 1 domain; an α-helix

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

Similar variants

RIGI p.Arg71Cys 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.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-arg71his (accessed [today's date]).

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