Is CAVIN2 p.Gln83His (c.249G>C) pathogenic?

CAVIN2 p.Gln83His (c.249G>C) is classified Uncertain significance in CAVIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.7878); Rare (popmax 0.253%, afr).

How common is CAVIN2 p.Gln83His (c.249G>C) in the general population?

CAVIN2 p.Gln83His (c.249G>C) is rare (popmax 0.253%, afr) (gnomAD).

What do computational predictors say about CAVIN2 p.Gln83His (c.249G>C)?

AlphaMissense predicts likely pathogenic (score 0.7878) — an in-silico prediction, not a clinical call.

CAVIN2 p.Gln83His

c.249G>C · VCV4219756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7878 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.253%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7878	likely pathogenic
REVEL	0.455	indeterminate
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.79 · regional, not allelic
Overall
CADD	24.9	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 0.253% African / African-American · 190/75,066 alleles

Filtering AF 0.224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0164% 265/1,614,228 alleles · rare exomes 142/1,461,882 · genomes 123/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.253%	395
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.0167%	6,003
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00415%	24,082

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.Gln83His
Coding: c.249G>C
MANE Select: NM_004657
Type: single nucleotide variant
Location: chr2:191846677 (GRCh38)
Gene constraint: LOEUF 1.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.48
Residue 83: the 'interaction with cavin1' region; the 'leucine-zipper' 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.Arg131His Uncertain significance ★ ⚠ same type
CAVIN2 p.Arg141Pro 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-gln83his (accessed [today's date]).

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