Is RINT1 p.Pro261= (c.783G>A) pathogenic?

RINT1 p.Pro261= (c.783G>A) is classified Benign in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-10). Rare (popmax 0.163%, afr).

How common is RINT1 p.Pro261= (c.783G>A) in the general population?

RINT1 p.Pro261= (c.783G>A) is rare (popmax 0.163%, afr) (gnomAD).

RINT1 p.Pro261=

c.783G>A · rs144905970 · VCV416398

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -6.5
Overall
CADD	0.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% African / African-American · 122/75,028 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.0104% 168/1,614,098 alleles · rare exomes 99/1,461,854 · genomes 69/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	615
Admixed American	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00254%	39,333

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.Pro261=
Coding: c.783G>A
MANE Select: NM_021930
dbSNP: rs144905970
Type: single nucleotide variant
Location: chr7:105547277 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 261: the rint1/tip20 domain

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

Similar variants

RINT1 p.Pro261Arg Uncertain significance ★★ ⚠ same residue
RINT1 p.Pro261Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RINT1 p.Pro261Ser 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

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-pro261 (accessed [today's date]).

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