Is RIN2 p.Ala617= (c.1851C>T) pathogenic?

RIN2 p.Ala617= (c.1851C>T) is classified Benign/Likely benign in RIN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.147%, eas); Associated with RIN2 syndrome.

What condition is associated with RIN2 p.Ala617= (c.1851C>T)?

RIN2 p.Ala617= (c.1851C>T) is associated with RIN2 syndrome (ClinVar).

How common is RIN2 p.Ala617= (c.1851C>T) in the general population?

RIN2 p.Ala617= (c.1851C>T) is rare (popmax 0.147%, eas) (gnomAD).

RIN2 p.Ala617=

c.1851C>T · rs180817901 · VCV509960

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, eas)

Conditions

RIN2 syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -5.4
Overall
CADD	5.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% East Asian · 65/44,296 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0787% 1,259/1,599,238 alleles · rare exomes 1,009/1,446,900 · genomes 250/152,338 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.49%	67
East Asiangrpmax	0.147%	681
Remaining individualsnot grpmax-eligible	0.0789%	1,267
Ashkenazi Jewishnot grpmax-eligible	0.0615%	1,625
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.0141%	7,109
Admixed American	0.0122%	8,184
South Asian	0.0113%	8,845
African / African-American	0.00668%	14,962

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala617=
Coding: c.1851C>T
MANE Select: NM_018993
dbSNP: rs180817901
Type: single nucleotide variant
Location: chr20:19990094 (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

Disease context

RIN2 syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIN2 p.Asn266Ile Uncertain significance ★★ ⚠ same condition
RIN2 p.His340Arg Uncertain significance ★★ ⚠ same condition
RIN2 p.Pro308Ala Uncertain significance ★★ ⚠ same condition
RIN2 p.Pro308Gln Uncertain significance ★★ ⚠ same condition
RIN2 p.Ser800Cys Uncertain significance ★★ ⚠ same condition
RIN2 p.Val840Ile Uncertain significance ★★ ⚠ same condition
RIN2 c.159-17G>A Likely benign ★★ same condition
RIN2 c.2201-47G>A Benign ★★ 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-ala617 (accessed [today's date]).

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