Is RIT1 p.Ter220= (c.659GAAGA[1]) pathogenic?

RIT1 p.Ter220= (c.659GAAGA[1]) is classified Uncertain significance in RIT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-04-26). Very rare (popmax 0.00111%, nfe).

How common is RIT1 p.Ter220= (c.659GAAGA[1]) in the general population?

RIT1 p.Ter220= (c.659GAAGA[1]) is very rare (popmax 0.00111%, nfe) (gnomAD).

RIT1 p.Ter220=

c.659GAAGA[1] · rs777195602 · VCV1098823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -3.9
Overall
CADD	9.285	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% European (non-Finnish) · 13/1,169,420 alleles

Filtering AF 0.00062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000478%

Overall 0.00106% 17/1,602,184 alleles · very rare exomes 16/1,450,004 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00644%	15,529
European (non-Finnish)grpmax	0.00111%	89,956

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RIT1
Protein: p.Ter220=
Coding: c.659GAAGA[1]
MANE Select: NM_006912
dbSNP: rs777195602
Type: Microsatellite
Location: chr1:155900380 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 3 PDB

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

Similar variants

RIT1 p.Asp66del Uncertain significance ★ same type
RIT1 p.Lys215fs Conflicting classifications of pathogenicity ★ ⚠ same type
RIT1 c.237+90CT[2] Likely benign ★ 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/rit1-p-ter220 (accessed [today's date]).

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