Is CAVIN1 p.Glu180= (c.540G>A) pathogenic?

CAVIN1 p.Glu180= (c.540G>A) is classified Conflicting classifications of pathogenicity in CAVIN1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-26). Rare (popmax 0.276%, nfe); Associated with congenital generalized lipodystrophy type 4.

What condition is associated with CAVIN1 p.Glu180= (c.540G>A)?

CAVIN1 p.Glu180= (c.540G>A) is associated with congenital generalized lipodystrophy type 4 (ClinVar).

How common is CAVIN1 p.Glu180= (c.540G>A) in the general population?

CAVIN1 p.Glu180= (c.540G>A) is rare (popmax 0.276%, nfe) (gnomAD).

CAVIN1 p.Glu180=

c.540G>A · rs143511306 · VCV436447

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.276%, nfe)

Conditions

congenital generalized lipodystrophy type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.65, phastCons 1
Overall
CADD	10.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% European (non-Finnish) · 3,261/1,179,978 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.215% 3,468/1,611,220 alleles · rare exomes 3,282/1,458,890 · genomes 186/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.276%	362
Remaining individualsnot grpmax-eligible	0.139%	718
Admixed American	0.0983%	1,018
African / African-American	0.0413%	2,422
Middle Eastern	0.033%	3,031
South Asian	0.0231%	4,337
Finnishnot grpmax-eligible	0.0115%	8,733

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: CAVIN1
Protein: p.Glu180=
Coding: c.540G>A
MANE Select: NM_012232
dbSNP: rs143511306
Type: single nucleotide variant
Location: chr17:42405320 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.03 · 3 PDB
Residue 180: the 'leucine-zipper 2' region; the 'disordered' region

Full CAVIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital generalized lipodystrophy type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAVIN1 c.*1110C>T Uncertain significance ★★ same condition
CAVIN1 c.*195C>G Uncertain significance ★★ same condition
CAVIN1 p.Ala21Val Uncertain significance ★★ ⚠ same condition
CAVIN1 p.Arg227Trp Uncertain significance ★★ ⚠ same condition
CAVIN1 p.Leu172Val Uncertain significance ★★ ⚠ same condition
CAVIN1 p.Pro283Ser Uncertain significance ★★ ⚠ same condition
CAVIN1 p.Thr279Arg Uncertain significance ★★ ⚠ same condition
CAVIN1 p.Val306Ala Uncertain significance ★★ ⚠ same condition

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/cavin1-p-glu180 (accessed [today's date]).

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