Is CAV2 p.Thr121= (c.363C>G) pathogenic?

CAV2 p.Thr121= (c.363C>G) is classified Likely benign in CAV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). Ultra-rare (popmax 0.0539%, sas).

How common is CAV2 p.Thr121= (c.363C>G) in the general population?

CAV2 p.Thr121= (c.363C>G) is ultra-rare (popmax 0.0539%, sas) (gnomAD).

CAV2 p.Thr121=

c.363C>G · VCV3485518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0539%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.178	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0539% South Asian · 49/90,864 alleles

Filtering AF 0.0419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0375%

Overall 0.00329% 53/1,612,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0539%	1,854
Remaining individualsnot grpmax-eligible	0.0032%	31,225
European (non-Finnish)	0.00017%	589,713

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.Thr121=
Coding: c.363C>G
MANE Select: NM_001233
Type: single nucleotide variant
Location: chr7:116505995 (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.Thr121Ala Uncertain significance ★ ⚠ same residue
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

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-thr121 (accessed [today's date]).

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