Is RINT1 p.Asp403His (c.1207G>C) pathogenic?

RINT1 p.Asp403His (c.1207G>C) is classified Uncertain significance in RINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-23). AlphaMissense: likely pathogenic (0.9771); Very rare (popmax 0.000169%, nfe).

How common is RINT1 p.Asp403His (c.1207G>C) in the general population?

RINT1 p.Asp403His (c.1207G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about RINT1 p.Asp403His (c.1207G>C)?

AlphaMissense predicts likely pathogenic (score 0.9771) — an in-silico prediction, not a clinical call.

RINT1 p.Asp403His

c.1207G>C · rs1289113738 · VCV937537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9771	likely pathogenic · top 5% in RINT1
REVEL	0.512	indeterminate
SaProt	LLR -13.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000169% European (non-Finnish) · 2/1,179,994 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,088 alleles · very rare exomes 2/1,461,816 · genomes 0/152,272 · joint denominator

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.Asp403His
Coding: c.1207G>C
MANE Select: NM_021930
dbSNP: rs1289113738
Type: single nucleotide variant
Location: chr7:105550360 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 403: the rint1/tip20 domain

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

Similar variants

RINT1 p.Asp403Asn Uncertain significance ★ ⚠ same residue
RINT1 p.Asp403Glu Uncertain significance ★ ⚠ same residue
RINT1 p.Asp403Gly Uncertain significance ★ ⚠ same residue
RINT1 p.Asp403Tyr Uncertain significance ★ ⚠ same residue
RINT1 p.Asp403Val Uncertain significance ★ ⚠ same residue
RINT1 p.Asp403= Likely benign ★ same residue
RINT1 p.Asp403fs Likely pathogenic ★ same residue
RINT1 c.1107+1G>T Likely pathogenic ★★ 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-asp403his (accessed [today's date]).

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