Is CAVIN4 p.Pro337Ala (c.1009C>G) pathogenic?

CAVIN4 p.Pro337Ala (c.1009C>G) is classified Uncertain significance in CAVIN4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely benign (0.0673); Absent from gnomAD v4.1; Associated with CAVIN4-related disorder.

What condition is associated with CAVIN4 p.Pro337Ala (c.1009C>G)?

CAVIN4 p.Pro337Ala (c.1009C>G) is associated with CAVIN4-related disorder (ClinVar).

How common is CAVIN4 p.Pro337Ala (c.1009C>G) in the general population?

CAVIN4 p.Pro337Ala (c.1009C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAVIN4 p.Pro337Ala (c.1009C>G)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

CAVIN4 p.Pro337Ala

c.1009C>G · VCV3347325

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CAVIN4-related disorder

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.14	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 1.1	GERP 2.2, phastCons 0.25
Regional constraint	o/e 1.04	unconstrained · MANE · 8,304 bp · p 0.38 · regional, not allelic
Overall
CADD	11.08	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAVIN4
Protein: p.Pro337Ala
Coding: c.1009C>G
MANE Select: NM_001018116
Type: single nucleotide variant
Location: chr9:100586365 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 66.21
Residue 337: 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.Val132Met Uncertain significance ⚠ same condition
CAVIN4 p.Asp160= Likely benign same condition
CAVIN4 p.Ala322fs Uncertain significance same condition
CAVIN4 p.Arg17Cys Uncertain significance ★★ ⚠ same type
CAVIN4 p.Arg272Cys Uncertain significance ★★ ⚠ same type
CAVIN4 p.Asn128Lys Uncertain significance ★★ ⚠ same type
CAVIN4 p.Pro142Leu Uncertain significance ★★ ⚠ same type
CAVIN4 p.Ser20Thr 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/cavin4-p-pro337ala (accessed [today's date]).

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