Is CAV2 p.Cys151Tyr (c.452G>A) pathogenic?

CAV2 p.Cys151Tyr (c.452G>A) is classified Uncertain significance in CAV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.294); Very rare (popmax 0.000763%, nfe).

How common is CAV2 p.Cys151Tyr (c.452G>A) in the general population?

CAV2 p.Cys151Tyr (c.452G>A) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about CAV2 p.Cys151Tyr (c.452G>A)?

AlphaMissense predicts likely benign (score 0.294) — an in-silico prediction, not a clinical call.

CAV2 p.Cys151Tyr

c.452G>A · rs1171200240 · VCV3137855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.294 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.294	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -4, phastCons 0.001
Regional constraint	o/e 1.10	unconstrained · MANE · 6,336 bp · p 0.16 · regional, not allelic
Overall
CADD	20.6	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 0.000763% European (non-Finnish) · 9/1,179,962 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,613,966 alleles · very rare

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: CAV2
Protein: p.Cys151Tyr
Coding: c.452G>A
MANE Select: NM_001233
dbSNP: rs1171200240
Type: single nucleotide variant
Location: chr7:116506084 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 78.26

Full CAV2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAV2 p.Ser147= Benign ★★ same type
CAV2 p.Ala8Val Uncertain significance ★ ⚠ same type
CAV2 p.Arg40Gln Uncertain significance ★ ⚠ same type
CAV2 p.Asp17Ala Uncertain significance ★ ⚠ same type
CAV2 p.Asp17Tyr Uncertain significance ★ ⚠ same type
CAV2 p.Asp55Asn Uncertain significance ★ ⚠ same type
CAV2 p.Gln158Lys Uncertain significance ★ ⚠ same type
CAV2 p.Glu26Ala 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/cav2-p-cys151tyr (accessed [today's date]).

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