Is CAVIN4 p.Arg249Lys (c.746G>A) pathogenic?

CAVIN4 p.Arg249Lys (c.746G>A) is classified Likely benign in CAVIN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: likely benign (0.0707); Absent from gnomAD v4.1.

How common is CAVIN4 p.Arg249Lys (c.746G>A) in the general population?

CAVIN4 p.Arg249Lys (c.746G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAVIN4 p.Arg249Lys (c.746G>A)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

CAVIN4 p.Arg249Lys

c.746G>A · rs1839474540 · VCV2532066

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.91	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 -0.12	GERP -3.4
Regional constraint	o/e 1.04	unconstrained · MANE · 8,304 bp · p 0.38 · regional, not allelic
Overall
CADD	6.199	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

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.Arg249Lys
Coding: c.746G>A
MANE Select: NM_001018116
dbSNP: rs1839474540
Type: single nucleotide variant
Location: chr9:100586102 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 66.21
Residue 249: the 'disordered' region

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

Similar variants

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
CAVIN4 c.408+28T>C Likely benign ★★ same type
CAVIN4 c.408+42T>C Benign ★★ same type
CAVIN4 c.408+6C>A 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-arg249lys (accessed [today's date]).

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