Is CAVIN2 p.Arg362Ser (c.1086G>C) pathogenic?

CAVIN2 p.Arg362Ser (c.1086G>C) is classified Uncertain significance in CAVIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1168); Ultra-rare (popmax 0.0757%, eas).

How common is CAVIN2 p.Arg362Ser (c.1086G>C) in the general population?

CAVIN2 p.Arg362Ser (c.1086G>C) is ultra-rare (popmax 0.0757%, eas) (gnomAD).

What do computational predictors say about CAVIN2 p.Arg362Ser (c.1086G>C)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

CAVIN2 p.Arg362Ser

c.1086G>C · rs377713440 · VCV3137872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0757%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -3.98	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 -0.79	GERP -3.8
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.79 · regional, not allelic
Overall
CADD	3.581	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 0.0757% East Asian · 34/44,886 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.00384% 62/1,614,212 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0757%	1,320
Remaining individualsnot grpmax-eligible	0.0288%	3,473
South Asian	0.00878%	11,385
European (non-Finnish)	0.000169%	590,012

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: CAVIN2
Protein: p.Arg362Ser
Coding: c.1086G>C
MANE Select: NM_004657
dbSNP: rs377713440
Type: single nucleotide variant
Location: chr2:191836115 (GRCh38)
Gene constraint: LOEUF 1.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.48
Residue 362: the 'disordered' region

Full CAVIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAVIN2 p.Lys173= Benign ★★ same type
CAVIN2 p.Val66= Benign ★★ same type
CAVIN2 p.Ala105Asp Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala137Val Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala309Thr Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala400Thr Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg131His Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg141Pro 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/cavin2-p-arg362ser (accessed [today's date]).

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