Is RINT1 p.Pro53Ser (c.157C>T) pathogenic?

RINT1 p.Pro53Ser (c.157C>T) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.0846); Very rare (popmax 0.00267%, afr).

How common is RINT1 p.Pro53Ser (c.157C>T) in the general population?

RINT1 p.Pro53Ser (c.157C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about RINT1 p.Pro53Ser (c.157C>T)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

RINT1 p.Pro53Ser

c.157C>T · rs1255155502 · VCV960740

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -4.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.87	GERP -6.1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	0.727	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,824 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,612,050 alleles · very rare exomes 4/1,459,996 · genomes 3/152,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,412
Admixed American	0.00167%	59,778
European (non-Finnish)	0.000339%	294,731

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.Pro53Ser
Coding: c.157C>T
MANE Select: NM_021930
dbSNP: rs1255155502
Type: single nucleotide variant
Location: chr7:105536633 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97

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

Similar variants

RINT1 p.Pro53Leu 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
RINT1 p.Ala13Val 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-pro53ser (accessed [today's date]).

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