Is RIN2 p.Ser479Phe (c.1436C>T) pathogenic?

RIN2 p.Ser479Phe (c.1436C>T) is classified Uncertain significance in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.2209); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with RIN2 p.Ser479Phe (c.1436C>T)?

RIN2 p.Ser479Phe (c.1436C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RIN2 p.Ser479Phe (c.1436C>T) in the general population?

RIN2 p.Ser479Phe (c.1436C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RIN2 p.Ser479Phe (c.1436C>T)?

AlphaMissense predicts likely benign (score 0.2209) — an in-silico prediction, not a clinical call.

RIN2 p.Ser479Phe

c.1436C>T · VCV3945917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2209	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.34	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	23.9	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 0.00133% African / African-American · 1/75,056 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,614,040 alleles · very rare exomes 11/1,461,710 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	0.000848%	117,990

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: RIN2
Protein: p.Ser479Phe
Coding: c.1436C>T
MANE Select: NM_018993
Type: single nucleotide variant
Location: chr20:19975461 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 479: the 'disordered' region

Full RIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same condition
RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg303Gln Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg446Gln 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/rin2-p-ser479phe (accessed [today's date]).

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