Is CAV2 p.Phe91Ser (c.272T>C) pathogenic?

CAV2 p.Phe91Ser (c.272T>C) is classified Uncertain significance in CAV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: ambiguous (0.4139); Very rare (popmax 0.000254%, nfe).

How common is CAV2 p.Phe91Ser (c.272T>C) in the general population?

CAV2 p.Phe91Ser (c.272T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CAV2 p.Phe91Ser (c.272T>C)?

AlphaMissense predicts ambiguous (score 0.4139) — an in-silico prediction, not a clinical call.

CAV2 p.Phe91Ser

c.272T>C · VCV4648671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4139	ambiguous
REVEL	0.737	pathogenic-leaning
SaProt	LLR -9.84	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 6,336 bp · p 0.16 · regional, not allelic
Overall
CADD	26.8	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 0.000254% European (non-Finnish) · 3/1,180,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,874 alleles · very rare

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.Phe91Ser
Coding: c.272T>C
MANE Select: NM_001233
Type: single nucleotide variant
Location: chr7:116500381 (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-phe91ser (accessed [today's date]).

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