Is RIN2 p.Ala205Val (c.614C>T) pathogenic?

RIN2 p.Ala205Val (c.614C>T) is classified Uncertain significance in RIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-20). AlphaMissense: ambiguous (0.4772); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RIN2 p.Ala205Val (c.614C>T)?

RIN2 p.Ala205Val (c.614C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RIN2 p.Ala205Val (c.614C>T) in the general population?

RIN2 p.Ala205Val (c.614C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about RIN2 p.Ala205Val (c.614C>T)?

AlphaMissense predicts ambiguous (score 0.4772) — an in-silico prediction, not a clinical call.

RIN2 p.Ala205Val

c.614C>T · rs547787195 · VCV2142564

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4772	ambiguous
REVEL	0.22	benign-leaning
SaProt	LLR -9.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	25.3	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 0.00161% European (non-Finnish) · 19/1,179,090 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,612,300 alleles · very rare exomes 16/1,460,052 · genomes 3/152,248 · joint denominator

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.Ala205Val
Coding: c.614C>T
MANE Select: NM_018993
dbSNP: rs547787195
Type: single nucleotide variant
Location: chr20:19970915 (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

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

Similar variants

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
RIN2 p.Arg516Gly 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-ala205val (accessed [today's date]).

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