Is CAVIN4 p.Pro324Leu (c.971C>T) pathogenic?

CAVIN4 p.Pro324Leu (c.971C>T) is classified Likely benign in CAVIN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). AlphaMissense: likely benign (0.0705); Rare (popmax 0.151%, afr).

How common is CAVIN4 p.Pro324Leu (c.971C>T) in the general population?

CAVIN4 p.Pro324Leu (c.971C>T) is rare (popmax 0.151%, afr) (gnomAD).

What do computational predictors say about CAVIN4 p.Pro324Leu (c.971C>T)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

CAVIN4 p.Pro324Leu

c.971C>T · rs147742000 · VCV516885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.83	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 -1.9	GERP -4.4
Regional constraint	o/e 1.04	unconstrained · MANE · 8,304 bp · p 0.38 · regional, not allelic
Overall
CADD	0.199	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

Grpmax group 0.151% African / African-American · 113/74,950 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.0115% 185/1,613,866 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.151%	663
Middle Eastern	0.0495%	2,021
East Asian	0.00892%	11,213
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.00466%	21,454
South Asian	0.00439%	22,761
Admixed American	0.00333%	30,006

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.Pro324Leu
Coding: c.971C>T
MANE Select: NM_001018116
dbSNP: rs147742000
Type: single nucleotide variant
Location: chr9:100586327 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 66.21
Residue 324: the 'disordered' region

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

Similar variants

CAVIN4 p.Pro324Arg Uncertain significance ★ ⚠ same residue
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

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-pro324leu (accessed [today's date]).

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