Is RINT1 p.Asp552His (c.1654G>C) pathogenic?

RINT1 p.Asp552His (c.1654G>C) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-03). AlphaMissense: likely pathogenic (0.8025); Absent from gnomAD v4.1.

How common is RINT1 p.Asp552His (c.1654G>C) in the general population?

RINT1 p.Asp552His (c.1654G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RINT1 p.Asp552His (c.1654G>C)?

AlphaMissense predicts likely pathogenic (score 0.8025) — an in-silico prediction, not a clinical call.

RINT1 p.Asp552His

c.1654G>C · rs1586250839 · VCV641090

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8025	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	30.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RINT1
Protein: p.Asp552His
Coding: c.1654G>C
MANE Select: NM_021930
dbSNP: rs1586250839
Type: single nucleotide variant
Location: chr7:105555210 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 552: the rint1/tip20 domain

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

Similar variants

RINT1 p.Asp552= Benign/Likely benign ★★ 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-asp552his (accessed [today's date]).

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