Is RIN2 p.Ser322Asn (c.965G>A) pathogenic?

RIN2 p.Ser322Asn (c.965G>A) is classified Benign/Likely benign in RIN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.1375); Low-frequency (popmax 1.83%, afr).

How common is RIN2 p.Ser322Asn (c.965G>A) in the general population?

RIN2 p.Ser322Asn (c.965G>A) is low-frequency (popmax 1.83%, afr) (gnomAD).

What do computational predictors say about RIN2 p.Ser322Asn (c.965G>A)?

AlphaMissense predicts likely benign (score 0.1375) — an in-silico prediction, not a clinical call.

RIN2 p.Ser322Asn

c.965G>A · rs199693970 · VCV436534

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1375 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1375	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.41	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 6.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	19.68	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 1.83% African / African-American · 1,104/60,310 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7%

Overall 0.0951% 1,271/1,336,970 alleles · low-frequency exomes 619/1,211,284 · genomes 652/125,686 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.83%	55
Remaining individualsnot grpmax-eligible	0.122%	822
Admixed American	0.116%	864
Middle Eastern	0.0421%	2,378
European (non-Finnish)	0.00516%	19,389
South Asian	0.00115%	87,118

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.Ser322Asn
Coding: c.965G>A
MANE Select: NM_018993
dbSNP: rs199693970
Type: single nucleotide variant
Location: chr20:19974990 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 322: the 'disordered' region

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-ser322asn (accessed [today's date]).

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