Is RINT1 p.Phe674fs (c.2021del) pathogenic?

RINT1 p.Phe674fs (c.2021del) is classified Pathogenic in RINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.0011%, sas).

How common is RINT1 p.Phe674fs (c.2021del) in the general population?

RINT1 p.Phe674fs (c.2021del) is very rare (popmax 0.0011%, sas) (gnomAD).

RINT1 p.Phe674fs

c.2021del · rs2133477788 · VCV1430736

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP 2.1, phastCons 0.002
Overall
CADD	25.4	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 0.0011% South Asian · 1/91,090 alleles

Overall 6.2e-05% 1/1,614,162 alleles · very rare exomes 0/1,461,866 · genomes 1/152,296 · 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: RINT1
Protein: p.Phe674fs
Coding: c.2021del
MANE Select: NM_021930
dbSNP: rs2133477788
Type: Deletion
Location: chr7:105565408 (GRCh38)

Full RINT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/rint1-p-phe674fs (accessed [today's date]).

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