Is CAVIN3 p.Val20Met (c.58G>A) pathogenic?

CAVIN3 p.Val20Met (c.58G>A) is classified Uncertain significance in CAVIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.5809); Very rare (popmax 0.00551%, afr).

How common is CAVIN3 p.Val20Met (c.58G>A) in the general population?

CAVIN3 p.Val20Met (c.58G>A) is very rare (popmax 0.00551%, afr) (gnomAD).

What do computational predictors say about CAVIN3 p.Val20Met (c.58G>A)?

AlphaMissense predicts likely pathogenic (score 0.5809) — an in-silico prediction, not a clinical call.

CAVIN3 p.Val20Met

c.58G>A · VCV4648687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5809	likely pathogenic
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,310 bp · p 0.029 · regional, not allelic
Overall
CADD	28.9	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 0.00551% African / African-American · 4/72,598 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00186%

Overall 0.00251% 39/1,554,916 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00551%	18,150
European (non-Finnish)	0.00294%	34,064
Admixed American	0.00187%	53,546

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: CAVIN3
Protein: p.Val20Met
Coding: c.58G>A
MANE Select: NM_145040
Type: single nucleotide variant
Location: chr11:6320419 (GRCh38)
Gene constraint: LOEUF 1.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.11
Residue 20: the 'interaction with cavin1' region; the 'leucine-zipper' region

Full CAVIN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAVIN3 p.Ala141Ser Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala218Gly Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala220Ser Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala227Val Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala249Ser Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala66Thr Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala94Thr Uncertain significance ★ ⚠ same type
CAVIN3 p.Ala95Val 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/cavin3-p-val20met (accessed [today's date]).

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