Is RINT1 p.Phe558= (c.1674C>T) pathogenic?

RINT1 p.Phe558= (c.1674C>T) is classified Likely benign in RINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Very rare (popmax 0.0017%, amr).

How common is RINT1 p.Phe558= (c.1674C>T) in the general population?

RINT1 p.Phe558= (c.1674C>T) is very rare (popmax 0.0017%, amr) (gnomAD).

RINT1 p.Phe558=

c.1674C>T · rs1159314611 · VCV1777758

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP 1.7, phastCons 0.99
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,958 alleles

Overall 0.000124% 2/1,609,502 alleles · very rare exomes 2/1,457,232 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,958
Remaining individualsnot grpmax-eligible	0.0016%	62,336

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.Phe558=
Coding: c.1674C>T
MANE Select: NM_021930
dbSNP: rs1159314611
Type: single nucleotide variant
Location: chr7:105563735 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 558: the rint1/tip20 domain

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

Similar variants

RINT1 p.Phe558Ser Uncertain significance ★★ ⚠ same residue
RINT1 p.Phe558Leu Uncertain significance ★ ⚠ same residue
RINT1 p.Phe558Val 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

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-phe558 (accessed [today's date]).

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