Is RIN1 p.Val293Ala (c.878T>C) pathogenic?

RIN1 p.Val293Ala (c.878T>C) is classified Uncertain significance in RIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0681); Very rare (popmax 0.00114%, sas).

How common is RIN1 p.Val293Ala (c.878T>C) in the general population?

RIN1 p.Val293Ala (c.878T>C) is very rare (popmax 0.00114%, sas) (gnomAD).

What do computational predictors say about RIN1 p.Val293Ala (c.878T>C)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

RIN1 p.Val293Ala

c.878T>C · VCV3945898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.10	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 0.24	GERP -2.5
Regional constraint	o/e 0.98	unconstrained · MANE · 4,123 bp · p 0.45 · regional, not allelic
Overall
CADD	6.365	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00114% South Asian · 1/87,900 alleles

Overall 6.3e-05% 1/1,586,908 alleles · very rare exomes 1/1,434,600 · genomes 0/152,308 · joint denominator

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: RIN1
Protein: p.Val293Ala
Coding: c.878T>C
MANE Select: NM_004292
Type: single nucleotide variant
Location: chr11:66334921 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.78

Full RIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIN1 p.Val293Met Uncertain significance ★ ⚠ same residue
RIN1 p.Ala690= Benign ★★ same type
RIN1 p.Gly737= Benign ★★ same type
RIN1 p.Thr643= Benign/Likely benign ★★ same type
RIN1 p.Val700Ile Benign ★★ same type
RIN1 p.Ala111Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala168Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala221Ser 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/rin1-p-val293ala (accessed [today's date]).

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