Is CAV1 p.Ile150Val (c.448A>G) pathogenic?

CAV1 p.Ile150Val (c.448A>G) is classified Conflicting classifications of pathogenicity in CAV1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.1015); Ultra-rare (popmax 0.0333%, amr); Associated with Inborn genetic diseases.

What condition is associated with CAV1 p.Ile150Val (c.448A>G)?

CAV1 p.Ile150Val (c.448A>G) is associated with Inborn genetic diseases, pulmonary hypertension, primary, 3 (ClinVar).

How common is CAV1 p.Ile150Val (c.448A>G) in the general population?

CAV1 p.Ile150Val (c.448A>G) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

What do computational predictors say about CAV1 p.Ile150Val (c.448A>G)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

CAV1 p.Ile150Val

c.448A>G · rs140936491 · VCV566670

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1015	likely benign
REVEL	0.469	indeterminate
SaProt	LLR -6.53	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 11	GERP 0.76, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 34 kb · p 0.17 · regional, not allelic
Overall
CADD	21.6	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 0.0333% Admixed American · 20/59,994 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00836% 135/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.105%	956
Admixed Americangrpmax	0.0333%	3,000
Remaining individualsnot grpmax-eligible	0.0112%	8,929
East Asian	0.00446%	22,439
European (non-Finnish)	0.00314%	31,889
African / African-American	0.00133%	75,042
South Asian	0.0011%	91,088

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAV1
Protein: p.Ile150Val
Coding: c.448A>G
MANE Select: NM_001753
dbSNP: rs140936491
Type: single nucleotide variant
Location: chr7:116559198 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.60 · 1 PDB
Residue 150: an α-helix; the 'interacts with spry1, spry2, and spry4' region

Full CAV1 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

Also linked: pulmonary hypertension, primary, 3

Similar variants

CAV1 p.Ile150fs Likely pathogenic ★ same residue
CAV1 c.30+3A>G Uncertain significance ★★ same condition
CAV1 p.Arg101His Uncertain significance ★★ ⚠ same condition
CAV1 p.Arg146His Uncertain significance ★★ ⚠ same condition
CAV1 p.Arg171His Uncertain significance ★★ ⚠ same condition
CAV1 p.Gly83Ser Uncertain significance ★★ ⚠ same condition
CAV1 p.His79Arg Uncertain significance ★★ ⚠ same condition
CAV1 p.Lys86Arg 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/cav1-p-ile150val (accessed [today's date]).

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