Is RINT1 p.Cys720Phe (c.2159G>T) pathogenic?

RINT1 p.Cys720Phe (c.2159G>T) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-26). AlphaMissense: ambiguous (0.4894); Very rare (popmax 0.00246%, nfe).

How common is RINT1 p.Cys720Phe (c.2159G>T) in the general population?

RINT1 p.Cys720Phe (c.2159G>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about RINT1 p.Cys720Phe (c.2159G>T)?

AlphaMissense predicts ambiguous (score 0.4894) — an in-silico prediction, not a clinical call.

RINT1 p.Cys720Phe

c.2159G>T · rs201892348 · VCV1042079

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

⚠ 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	0.4894	ambiguous
REVEL	0.562	indeterminate
SaProt	LLR -10.71	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 3.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	29.2	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

Grpmax group 0.00246% European (non-Finnish) · 29/1,177,466 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00211% 34/1,610,562 alleles · very rare exomes 32/1,458,450 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00642%	15,587
European (non-Finnish)grpmax	0.00246%	40,602
Admixed American	0.00167%	59,780

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: RINT1
Protein: p.Cys720Phe
Coding: c.2159G>T
MANE Select: NM_021930
dbSNP: rs201892348
Type: single nucleotide variant
Location: chr7:105565621 (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-cys720phe (accessed [today's date]).

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