Is RINT1 p.Val217Phe (c.649G>T) pathogenic?

RINT1 p.Val217Phe (c.649G>T) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.667); Absent from gnomAD v4.1.

How common is RINT1 p.Val217Phe (c.649G>T) in the general population?

RINT1 p.Val217Phe (c.649G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RINT1 p.Val217Phe (c.649G>T)?

AlphaMissense predicts likely pathogenic (score 0.667) — an in-silico prediction, not a clinical call.

RINT1 p.Val217Phe

c.649G>T · rs878855074 · VCV241413

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.667 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.667	likely pathogenic
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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: RINT1
Protein: p.Val217Phe
Coding: c.649G>T
MANE Select: NM_021930
dbSNP: rs878855074
Type: single nucleotide variant
Location: chr7:105547043 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97

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

Similar variants

RINT1 p.Val217Ala Uncertain significance ★ ⚠ same residue
RINT1 p.Val217Ile Uncertain significance ★ ⚠ same residue
RINT1 p.Val217= Likely benign ★ same residue
RINT1 c.1107+1G>T Likely pathogenic ★★ same type
RINT1 c.1886+5G>A Uncertain significance ★★ same type
RINT1 c.516-3C>T Uncertain significance ★★ same type
RINT1 c.840-12T>A Uncertain significance ★★ same type
RINT1 c.840-3C>G 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/rint1-p-val217phe (accessed [today's date]).

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