Is CAVIN4 p.Ala322fs (c.963del) pathogenic?

CAVIN4 p.Ala322fs (c.963del) is classified Uncertain significance in CAVIN4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-27). Ultra-rare (popmax 0.0183%, amr); Associated with CAVIN4-related disorder.

What condition is associated with CAVIN4 p.Ala322fs (c.963del)?

CAVIN4 p.Ala322fs (c.963del) is associated with CAVIN4-related disorder (ClinVar).

How common is CAVIN4 p.Ala322fs (c.963del) in the general population?

CAVIN4 p.Ala322fs (c.963del) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

CAVIN4 p.Ala322fs

c.963del · VCV3354368

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

CAVIN4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -2.3
Overall
CADD	16.68	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,970 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.000682% 11/1,613,756 alleles · ultra-rare exomes 10/1,461,636 · genomes 1/152,120 · joint denominator

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: CAVIN4
Protein: p.Ala322fs
Coding: c.963del
MANE Select: NM_001018116
Type: Deletion
Location: chr9:100586319 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 66.21
Residue 322: the 'disordered' region

Full CAVIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAVIN4-related disorder

Similar variants

CAVIN4 p.Pro337Ala Uncertain significance ⚠ same condition
CAVIN4 p.Val132Met Uncertain significance ⚠ same condition
CAVIN4 p.Asp160= Likely benign same condition
CAVIN4 p.Ser251fs Uncertain significance ★ same type
CAVIN4 p.234LRQSGER[2] Likely benign ★ 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/cavin4-p-ala322fs (accessed [today's date]).

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