Is RINT1 p.Arg104Ter (c.310C>T) pathogenic?

RINT1 p.Arg104Ter (c.310C>T) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-11-11). Very rare (popmax 0.000594%, nfe).

How common is RINT1 p.Arg104Ter (c.310C>T) in the general population?

RINT1 p.Arg104Ter (c.310C>T) is very rare (popmax 0.000594%, nfe) (gnomAD).

RINT1 p.Arg104Ter

c.310C>T · rs777242801 · VCV657219

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,177,754 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,611,150 alleles · very rare exomes 6/1,459,038 · genomes 1/152,112 · 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.Arg104Ter
Coding: c.310C>T
MANE Select: NM_021930
dbSNP: rs777242801
Type: single nucleotide variant
Location: chr7:105542444 (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.Arg104Gly Uncertain significance ★★ ⚠ same residue
RINT1 p.Arg104= Likely benign ★★ same residue
RINT1 p.Arg104Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RINT1 p.Arg104Leu 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-arg104ter (accessed [today's date]).

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