Is CAVIN3 p.Pro209Leu (c.626C>T) pathogenic?

CAVIN3 p.Pro209Leu (c.626C>T) is classified Uncertain significance in CAVIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely benign (0.2028); Ultra-rare (popmax 0.0362%, afr).

How common is CAVIN3 p.Pro209Leu (c.626C>T) in the general population?

CAVIN3 p.Pro209Leu (c.626C>T) is ultra-rare (popmax 0.0362%, afr) (gnomAD).

What do computational predictors say about CAVIN3 p.Pro209Leu (c.626C>T)?

AlphaMissense predicts likely benign (score 0.2028) — an in-silico prediction, not a clinical call.

CAVIN3 p.Pro209Leu

c.626C>T · rs543801330 · VCV3137909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2028 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2028	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.69	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,310 bp · p 0.029 · regional, not allelic
Overall
CADD	29.4	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

Grpmax group 0.0362% African / African-American · 27/74,542 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.022%

Overall 0.00224% 36/1,604,196 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0362%	2,761
East Asian	0.00894%	11,192
Remaining individualsnot grpmax-eligible	0.00485%	20,635
South Asian	0.00111%	89,864
European (non-Finnish)	8.51e-05%	1,175,746

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.Pro209Leu
Coding: c.626C>T
MANE Select: NM_145040
dbSNP: rs543801330
Type: single nucleotide variant
Location: chr11:6319323 (GRCh38)
Gene constraint: LOEUF 1.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.11
Residue 209: the 'disordered' 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-pro209leu (accessed [today's date]).

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