Is RIN2 p.Glu203Asp (c.609A>T) pathogenic?

RIN2 p.Glu203Asp (c.609A>T) is classified Likely benign in RIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.097); Rare (popmax 0.486%, eas).

How common is RIN2 p.Glu203Asp (c.609A>T) in the general population?

RIN2 p.Glu203Asp (c.609A>T) is rare (popmax 0.486%, eas) (gnomAD).

What do computational predictors say about RIN2 p.Glu203Asp (c.609A>T)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

RIN2 p.Glu203Asp

c.609A>T · rs180853961 · VCV668349

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.486%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.35	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 5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	17.69	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 0.486% East Asian · 218/44,856 alleles

Filtering AF 0.433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.413%

Overall 0.0151% 244/1,612,970 alleles · rare exomes 208/1,460,676 · genomes 36/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.486%	206
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,940
South Asian	0.011%	9,065
European (non-Finnish)	0.000509%	196,584

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.Glu203Asp
Coding: c.609A>T
MANE Select: NM_018993
dbSNP: rs180853961
Type: single nucleotide variant
Location: chr20:19970910 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30

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

Similar variants

RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same type
RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same type
RIN2 p.Ala8Thr Uncertain significance ★★ ⚠ same type
RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same type
RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same type
RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same type
RIN2 p.Arg303Gln 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/rin2-p-glu203asp (accessed [today's date]).

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