Is RIN1 p.Ser485Ile (c.1454G>T) pathogenic?

RIN1 p.Ser485Ile (c.1454G>T) is classified Uncertain significance in RIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.1323); Very rare (popmax 0.00537%, afr).

How common is RIN1 p.Ser485Ile (c.1454G>T) in the general population?

RIN1 p.Ser485Ile (c.1454G>T) is very rare (popmax 0.00537%, afr) (gnomAD).

What do computational predictors say about RIN1 p.Ser485Ile (c.1454G>T)?

AlphaMissense predicts likely benign (score 0.1323) — an in-silico prediction, not a clinical call.

RIN1 p.Ser485Ile

c.1454G>T · rs749622372 · VCV2327836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00537%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1323	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 1.4, phastCons 0.35
Regional constraint	o/e 0.98	unconstrained · MANE · 4,123 bp · p 0.45 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00537% African / African-American · 4/74,514 alleles

Filtering AF 0.00219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00194%

Overall 0.00261% 41/1,573,640 alleles · very rare exomes 35/1,421,462 · genomes 6/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00537%	18,628
European (non-Finnish)	0.00302%	33,159
Admixed American	0.00189%	52,844
Remaining individualsnot grpmax-eligible	0.00164%	60,966

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: RIN1
Protein: p.Ser485Ile
Coding: c.1454G>T
MANE Select: NM_004292
dbSNP: rs749622372
Type: single nucleotide variant
Location: chr11:66334056 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.78
Residue 485: the vps9 domain; the 'ras and 14-3-3 protein binding region' region

Full RIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIN1 p.Ala690= Benign ★★ same type
RIN1 p.Gly737= Benign ★★ same type
RIN1 p.Thr643= Benign/Likely benign ★★ same type
RIN1 p.Val700Ile Benign ★★ same type
RIN1 p.Ala111Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala168Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala221Ser Uncertain significance ★ ⚠ same type
RIN1 p.Ala31Val 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/rin1-p-ser485ile (accessed [today's date]).

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