Is RINT1 p.Ile779Phe (c.2335A>T) pathogenic?

RINT1 p.Ile779Phe (c.2335A>T) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-26). AlphaMissense: ambiguous (0.3604); Very rare (popmax 0.00187%, nfe).

How common is RINT1 p.Ile779Phe (c.2335A>T) in the general population?

RINT1 p.Ile779Phe (c.2335A>T) is very rare (popmax 0.00187%, nfe) (gnomAD).

What do computational predictors say about RINT1 p.Ile779Phe (c.2335A>T)?

AlphaMissense predicts ambiguous (score 0.3604) — an in-silico prediction, not a clinical call.

RINT1 p.Ile779Phe

c.2335A>T · rs1296819896 · VCV1442312

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

⚠ 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
AlphaMissense	0.3604	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -8.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.2	GERP 3.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.00187% European (non-Finnish) · 22/1,178,728 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,609,196 alleles · very rare exomes 22/1,456,936 · genomes 1/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,579
Remaining individualsnot grpmax-eligible	0.0016%	62,354

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.Ile779Phe
Coding: c.2335A>T
MANE Select: NM_021930
dbSNP: rs1296819896
Type: single nucleotide variant
Location: chr7:105567267 (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-ile779phe (accessed [today's date]).

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