Is CAVIN4 p.Arg17Cys (c.49C>T) pathogenic?

CAVIN4 p.Arg17Cys (c.49C>T) is classified Uncertain significance in CAVIN4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-21). AlphaMissense: likely benign (0.2434); Ultra-rare (popmax 0.03%, amr).

How common is CAVIN4 p.Arg17Cys (c.49C>T) in the general population?

CAVIN4 p.Arg17Cys (c.49C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about CAVIN4 p.Arg17Cys (c.49C>T)?

AlphaMissense predicts likely benign (score 0.2434) — an in-silico prediction, not a clinical call.

CAVIN4 p.Arg17Cys

c.49C>T · rs373690575 · VCV1220411

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2434	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -9.17	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 8,304 bp · p 0.38 · 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 0.03% Admixed American · 18/59,994 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.01% 162/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Middle Eastern	0.0164%	6,082
European (non-Finnish)	0.0112%	8,939
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.00401%	24,967
South Asian	0.0022%	45,528

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.Arg17Cys
Coding: c.49C>T
MANE Select: NM_001018116
dbSNP: rs373690575
Type: single nucleotide variant
Location: chr9:100578192 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 66.21
Residue 17: the 'disordered' region

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

Similar variants

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
CAVIN4 c.409-26T>A Likely 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-arg17cys (accessed [today's date]).

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