Is RINT1 p.Ile60Val (c.178A>G) pathogenic?

RINT1 p.Ile60Val (c.178A>G) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0765); Very rare (popmax 0.00223%, eas).

How common is RINT1 p.Ile60Val (c.178A>G) in the general population?

RINT1 p.Ile60Val (c.178A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RINT1 p.Ile60Val (c.178A>G)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

RINT1 p.Ile60Val

c.178A>G · rs745420669 · VCV410806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	13.08	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00223% East Asian · 1/44,838 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00093% 15/1,612,836 alleles · very rare exomes 12/1,460,622 · genomes 3/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,838
Remaining individualsnot grpmax-eligible	0.0016%	62,436
African / African-American	0.00134%	74,906
European (non-Finnish)	0.00102%	98,264

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.Ile60Val
Coding: c.178A>G
MANE Select: NM_021930
dbSNP: rs745420669
Type: single nucleotide variant
Location: chr7:105536654 (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.Ile60Met Uncertain significance ★ ⚠ same residue
RINT1 p.Ile60Thr 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
RINT1 p.Ala138Thr 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-ile60val (accessed [today's date]).

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