Is CAV2 p.Val148Ile (c.442G>A) pathogenic?

CAV2 p.Val148Ile (c.442G>A) is classified Uncertain significance in CAV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.029%, eas).

How common is CAV2 p.Val148Ile (c.442G>A) in the general population?

CAV2 p.Val148Ile (c.442G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CAV2 p.Val148Ile (c.442G>A)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CAV2 p.Val148Ile

c.442G>A · rs139300375 · VCV2378199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -6.27	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 -0.45	GERP -3.7
Regional constraint	o/e 1.10	unconstrained · MANE · 6,336 bp · p 0.16 · regional, not allelic
Overall
CADD	0.836	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 0.029% East Asian · 13/44,872 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0128% 207/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
European (non-Finnish)	0.0152%	6,592
South Asian	0.00878%	11,384
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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.Val148Ile
Coding: c.442G>A
MANE Select: NM_001233
dbSNP: rs139300375
Type: single nucleotide variant
Location: chr7:116506074 (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.Cys151Tyr Uncertain significance ★ ⚠ same type
CAV2 p.Gln158Lys 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-val148ile (accessed [today's date]).

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