Is RINT1 p.Pro246= (c.738C>T) pathogenic?

RINT1 p.Pro246= (c.738C>T) is classified Likely benign in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-25). Very rare (popmax 0.00267%, afr).

How common is RINT1 p.Pro246= (c.738C>T) in the general population?

RINT1 p.Pro246= (c.738C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

RINT1 p.Pro246=

c.738C>T · rs555764782 · VCV1616608

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -2.3
Overall
CADD	5.525	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,016 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,138 alleles · very rare exomes 0/1,461,866 · genomes 3/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,508
Admixed American	0.00167%	60,016

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.Pro246=
Coding: c.738C>T
MANE Select: NM_021930
dbSNP: rs555764782
Type: single nucleotide variant
Location: chr7:105547232 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 246: the rint1/tip20 domain

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

Similar variants

RINT1 p.Pro246Thr Likely benign ★★ same residue
RINT1 p.Pro246Ala Uncertain significance ★ ⚠ same residue
RINT1 p.Pro246Leu Uncertain significance ★ ⚠ same residue
RINT1 p.Pro246Ser 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

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-pro246 (accessed [today's date]).

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