Is CAVIN2 p.Arg131His (c.392G>A) pathogenic?

CAVIN2 p.Arg131His (c.392G>A) is classified Uncertain significance in CAVIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.2562); Very rare (popmax 0.004%, afr).

How common is CAVIN2 p.Arg131His (c.392G>A) in the general population?

CAVIN2 p.Arg131His (c.392G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CAVIN2 p.Arg131His (c.392G>A)?

AlphaMissense predicts likely benign (score 0.2562) — an in-silico prediction, not a clinical call.

CAVIN2 p.Arg131His

c.392G>A · VCV4219757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2562	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.79 · regional, not allelic
Overall
CADD	29.4	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 0.004% African / African-American · 3/74,952 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000434% 7/1,614,144 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,984
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,096
European (non-Finnish)	0.000169%	590,033

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.Arg131His
Coding: c.392G>A
MANE Select: NM_004657
Type: single nucleotide variant
Location: chr2:191846534 (GRCh38)
Gene constraint: LOEUF 1.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.48
Residue 131: 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.Ala137Val Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala309Thr Uncertain significance ★ ⚠ same type
CAVIN2 p.Ala400Thr 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-arg131his (accessed [today's date]).

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