Is RINT1 p.Leu560= (c.1680A>G) pathogenic?

RINT1 p.Leu560= (c.1680A>G) is classified Likely benign in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-17). Very rare (popmax 0.000424%, nfe).

How common is RINT1 p.Leu560= (c.1680A>G) in the general population?

RINT1 p.Leu560= (c.1680A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

RINT1 p.Leu560=

c.1680A>G · rs769025020 · VCV1113096

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.1	GERP -2.5, phastCons 0.016
Overall
CADD	3.786	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,142 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000558% 9/1,611,786 alleles · very rare exomes 9/1,459,472 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,341
Remaining individualsnot grpmax-eligible	0.0016%	62,436
European (non-Finnish)grpmax	0.000424%	235,828

Finnish 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.Leu560=
Coding: c.1680A>G
MANE Select: NM_021930
dbSNP: rs769025020
Type: single nucleotide variant
Location: chr7:105563741 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 560: the rint1/tip20 domain

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

Similar variants

RINT1 p.Leu560Gln Uncertain significance ★ ⚠ same residue
RINT1 p.Leu560Ile Uncertain significance ★ 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
RINT1 p.Ala138Thr 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-leu560 (accessed [today's date]).

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