Is CAVIN2 p.Ala137Val (c.410C>T) pathogenic?

CAVIN2 p.Ala137Val (c.410C>T) is classified Uncertain significance in CAVIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0905); Ultra-rare (popmax 0.02%, eas).

How common is CAVIN2 p.Ala137Val (c.410C>T) in the general population?

CAVIN2 p.Ala137Val (c.410C>T) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about CAVIN2 p.Ala137Val (c.410C>T)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

CAVIN2 p.Ala137Val

c.410C>T · rs752281751 · VCV3137875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.88	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 3.1	GERP 1.1, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.79 · regional, not allelic
Overall
CADD	12.43	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 0.02% East Asian · 9/44,898 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000558% 9/1,614,150 alleles · ultra-rare exomes 7/1,461,878 · genomes 2/152,272 · joint denominator

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: CAVIN2
Protein: p.Ala137Val
Coding: c.410C>T
MANE Select: NM_004657
dbSNP: rs752281751
Type: single nucleotide variant
Location: chr2:191846516 (GRCh38)
Gene constraint: LOEUF 1.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.48
Residue 137: the 'interaction with cavin1' region

Full CAVIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAVIN2 p.Lys173= Benign ★★ same type
CAVIN2 p.Val66= Benign ★★ same type
CAVIN2 p.Ala105Asp Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala309Thr Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala400Thr Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg131His Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg141Pro Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg151Gln 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/cavin2-p-ala137val (accessed [today's date]).

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