Is CAV2 p.Pro42Ser (c.124C>T) pathogenic?

CAV2 p.Pro42Ser (c.124C>T) is classified Uncertain significance in CAV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.3126); Ultra-rare (popmax 0.0156%, nfe).

How common is CAV2 p.Pro42Ser (c.124C>T) in the general population?

CAV2 p.Pro42Ser (c.124C>T) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

What do computational predictors say about CAV2 p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely benign (score 0.3126) — an in-silico prediction, not a clinical call.

CAV2 p.Pro42Ser

c.124C>T · rs374156174 · VCV2398616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3126	likely benign
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -10.55	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 6,336 bp · p 0.16 · regional, not allelic
Overall
CADD	26.9	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 0.0156% European (non-Finnish) · 184/1,179,492 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0115% 186/1,611,956 alleles · ultra-rare exomes 175/1,459,878 · genomes 11/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,410
Remaining individualsnot grpmax-eligible	0.00321%	31,196

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: CAV2
Protein: p.Pro42Ser
Coding: c.124C>T
MANE Select: NM_001233
dbSNP: rs374156174
Type: single nucleotide variant
Location: chr7:116499905 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 78.26

Full CAV2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAV2 p.Ser147= Benign ★★ same type
CAV2 p.Ala8Val Uncertain significance ★ ⚠ same type
CAV2 p.Arg40Gln Uncertain significance ★ ⚠ same type
CAV2 p.Asp17Ala Uncertain significance ★ ⚠ same type
CAV2 p.Asp17Tyr Uncertain significance ★ ⚠ same type
CAV2 p.Asp55Asn Uncertain significance ★ ⚠ same type
CAV2 p.Cys151Tyr Uncertain significance ★ ⚠ same type
CAV2 p.Gln158Lys 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/cav2-p-pro42ser (accessed [today's date]).

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