Is RINT1 p.Arg519Ter (c.1555C>T) pathogenic?

RINT1 p.Arg519Ter (c.1555C>T) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-11-17). Very rare (popmax 0.00446%, eas); Associated with infantile liver failure syndrome 3.

What condition is associated with RINT1 p.Arg519Ter (c.1555C>T)?

RINT1 p.Arg519Ter (c.1555C>T) is associated with infantile liver failure syndrome 3 (ClinVar).

How common is RINT1 p.Arg519Ter (c.1555C>T) in the general population?

RINT1 p.Arg519Ter (c.1555C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

RINT1 p.Arg519Ter

Q: How is Fever-associated acute infantile liver failure syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1555C>T · rs759853907 · VCV1449407

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

infantile liver failure syndrome 3

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 11 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 3.6, phastCons 1
Overall
CADD	40.0	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 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00192% 31/1,613,812 alleles · very rare exomes 26/1,461,648 · genomes 5/152,164 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
European (non-Finnish)	0.00229%	43,701
African / African-American	0.00134%	74,904
South Asian	0.0011%	91,082

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.Arg519Ter
Coding: c.1555C>T
MANE Select: NM_021930
dbSNP: rs759853907
Type: single nucleotide variant
Location: chr7:105555111 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 519: the rint1/tip20 domain

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

Disease context

infantile liver failure syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fever-associated acute infantile liver failure syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

RINT1 p.Arg519= Likely benign ★ same residue
RINT1 c.840-12T>A Uncertain significance ★★ same condition
RINT1 p.Arg374Trp Uncertain significance ★★ same condition
RINT1 p.Asp477His Uncertain significance ★★ ⚠ same condition
RINT1 p.Cys537Arg Uncertain significance ★★ ⚠ same condition
RINT1 p.His613Asn Uncertain significance ★★ ⚠ same condition
RINT1 p.Leu107Val Uncertain significance ★★ ⚠ same condition
RINT1 p.Leu406Ile Uncertain significance ★★ ⚠ same condition

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-arg519ter (accessed [today's date]).

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