Is RIT1 p.Val121= (c.363C>T) pathogenic?

RIT1 p.Val121= (c.363C>T) is classified Likely benign in RIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with RIT1 p.Val121= (c.363C>T)?

RIT1 p.Val121= (c.363C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is RIT1 p.Val121= (c.363C>T) in the general population?

RIT1 p.Val121= (c.363C>T) is absent from gnomAD v4.1 (gnomAD).

RIT1 p.Val121=

c.363C>T · VCV3433830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -4.2, phastCons 0.99
Overall
CADD	6.3	PHRED · no single calibrated threshold — expert panels disagree

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: RIT1
Protein: p.Val121=
Coding: c.363C>T
MANE Select: NM_006912
Type: single nucleotide variant
Location: chr1:155904377 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 3 PDB
Residue 121: an α-helix

Full RIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIT1 p.Ala77Gly Pathogenic/Likely pathogenic ★★ same condition
RIT1 p.Lys23Gln Pathogenic/Likely pathogenic ★★ same condition
RIT1 p.Phe82Val Pathogenic ★★ same condition
RIT1 p.Ala151Val Uncertain significance ★★ ⚠ same condition
RIT1 p.Ala16Thr Uncertain significance ★★ ⚠ same condition
RIT1 p.Ala192Val Uncertain significance ★★ ⚠ same condition
RIT1 p.Arg105Cys Uncertain significance ★★ ⚠ same condition
RIT1 p.Arg120Gln 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/rit1-p-val121 (accessed [today's date]).

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