Is CAV3 p.Phe41= (c.123T>C) pathogenic?

CAV3 p.Phe41= (c.123T>C) is classified Benign/Likely benign in CAV3 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Common (popmax 29%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Phe41= (c.123T>C)?

CAV3 p.Phe41= (c.123T>C) is associated with Cardiovascular phenotype, long QT syndrome, caveolinopathy (ClinVar).

CAV3 p.Phe41=

Q: How common is CAV3 p.Phe41= (c.123T>C) in the general population?

CAV3 p.Phe41= (c.123T>C) is common (popmax 29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.123T>C · rs13087941 · VCV31717

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 29%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.5	GERP -5.3
Overall
CADD	0.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29% African / African-American · 21,696/74,932 alleles

Filtering AF 28.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.5%

Overall 22.2% 358,479/1,612,768 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	29%	3
Finnishnot grpmax-eligible	26.3%	4
European (non-Finnish)	24.4%	4
Remaining individualsnot grpmax-eligible	20.2%	5
Amishnot grpmax-eligible	17%	6
Ashkenazi Jewishnot grpmax-eligible	15.4%	7
Admixed American	12.1%	8
Middle Eastern	10.3%	10
South Asian	6.92%	14
East Asian	0.428%	234

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: CAV3
Protein: p.Phe41=
Coding: c.123T>C
MANE Select: NM_033337
dbSNP: rs13087941
Type: single nucleotide variant
Location: chr3:8745534 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54

Full CAV3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome caveolinopathy rippling muscle disease 2

Similar variants

CAV3 c.114+2T>C Pathogenic ★★ same condition
CAV3 p.Ala46Thr Pathogenic/Likely pathogenic ★★ same condition
CAV3 p.Arg27Gln Pathogenic ★★ same condition
CAV3 p.Trp71Ter Pathogenic/Likely pathogenic ★★ same condition
CAV3 c.114+5G>C Uncertain significance ★★ same condition
CAV3 c.*134G>A Uncertain significance ★★ same condition
CAV3 c.*592G>A Uncertain significance ★★ same condition
CAV3 c.*658T>A Uncertain significance ★★ same condition

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/cav3-p-phe41 (accessed [today's date]).

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