Is RIGI p.Asp701Val (c.2102A>T) pathogenic?

RIGI p.Asp701Val (c.2102A>T) is classified Uncertain significance in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.9055); Absent from gnomAD v4.1.

How common is RIGI p.Asp701Val (c.2102A>T) in the general population?

RIGI p.Asp701Val (c.2102A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RIGI p.Asp701Val (c.2102A>T)?

AlphaMissense predicts likely pathogenic (score 0.9055) — an in-silico prediction, not a clinical call.

RIGI p.Asp701Val

c.2102A>T · rs376791494 · VCV1941520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9055 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9055	likely pathogenic · top 7% in RIGI
REVEL	0.487	indeterminate
SaProt	LLR -11.23	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 7.4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 1,504 bp · p 9.3e-05 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp701Val
Coding: c.2102A>T
MANE Select: NM_014314
dbSNP: rs376791494
Type: single nucleotide variant
Location: chr9:32467845 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 701: a β-strand; the helicase c-terminal domain; the 'interaction with zc3hav1' region

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

Similar variants

RIGI p.Asp701Ala Uncertain significance ★★ ⚠ same residue
RIGI p.Asp701Gly 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

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-asp701val (accessed [today's date]).

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