Is RIGI p.Asp910Tyr (c.2728G>T) pathogenic?

RIGI p.Asp910Tyr (c.2728G>T) is classified Conflicting classifications of pathogenicity in RIGI (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1159); Ultra-rare (popmax 0.036%, afr); Associated with Inborn genetic diseases.

What condition is associated with RIGI p.Asp910Tyr (c.2728G>T)?

RIGI p.Asp910Tyr (c.2728G>T) is associated with Inborn genetic diseases, Singleton-Merten syndrome 2 (ClinVar).

How common is RIGI p.Asp910Tyr (c.2728G>T) in the general population?

RIGI p.Asp910Tyr (c.2728G>T) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about RIGI p.Asp910Tyr (c.2728G>T)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

RIGI p.Asp910Tyr

c.2728G>T · rs377348789 · VCV1039146

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 0.44, phastCons 0.37
Regional constraint	o/e 1.01	unconstrained · MANE · 9,257 bp · p 0.84 · regional, not allelic
Overall
CADD	22.7	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 0.036% African / African-American · 27/75,028 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00421% 68/1,613,962 alleles · ultra-rare exomes 51/1,461,720 · genomes 17/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,779
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.00322%	31,051

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.Asp910Tyr
Coding: c.2728G>T
MANE Select: NM_014314
dbSNP: rs377348789
Type: single nucleotide variant
Location: chr9:32457172 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 910: an α-helix; 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Singleton-Merten syndrome 2

Similar variants

RIGI p.Asp910Glu Uncertain significance ★ ⚠ same residue
RIGI p.Asp910= Likely benign ★ same residue
RIGI p.Ala436Val Uncertain significance ★★ ⚠ same condition
RIGI p.Ala537Ser Uncertain significance ★★ ⚠ same condition
RIGI p.Ala537Thr Uncertain significance ★★ ⚠ same condition
RIGI p.Ala774Thr Uncertain significance ★★ ⚠ same condition
RIGI p.Arg109Cys Uncertain significance ★★ ⚠ same condition
RIGI p.Arg34Gly Uncertain significance ★★ ⚠ same condition

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-asp910tyr (accessed [today's date]).

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