Is CAVIN2 p.Val200Met (c.598G>A) pathogenic?

CAVIN2 p.Val200Met (c.598G>A) is classified Uncertain significance in CAVIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.2968); Very rare (popmax 0.00407%, nfe).

How common is CAVIN2 p.Val200Met (c.598G>A) in the general population?

CAVIN2 p.Val200Met (c.598G>A) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about CAVIN2 p.Val200Met (c.598G>A)?

AlphaMissense predicts likely benign (score 0.2968) — an in-silico prediction, not a clinical call.

CAVIN2 p.Val200Met

c.598G>A · rs745440132 · VCV3137888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2968	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.98	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 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.79 · regional, not allelic
Overall
CADD	26.5	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 0.00407% European (non-Finnish) · 48/1,180,034 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00322% 52/1,614,040 alleles · very rare exomes 49/1,461,888 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,584
Admixed American	0.00333%	30,004
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,080

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.Val200Met
Coding: c.598G>A
MANE Select: NM_004657
dbSNP: rs745440132
Type: single nucleotide variant
Location: chr2:191836603 (GRCh38)
Gene constraint: LOEUF 1.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.48
Residue 200: 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-val200met (accessed [today's date]).

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