Is CAVIN1 p.Ala309= (c.927G>A) pathogenic?

CAVIN1 p.Ala309= (c.927G>A) is classified Benign in CAVIN1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-31). Common (popmax 5.97%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital generalized lipodystrophy type 4.

What condition is associated with CAVIN1 p.Ala309= (c.927G>A)?

CAVIN1 p.Ala309= (c.927G>A) is associated with congenital generalized lipodystrophy type 4 (ClinVar).

CAVIN1 p.Ala309=

Q: How common is CAVIN1 p.Ala309= (c.927G>A) in the general population?

CAVIN1 p.Ala309= (c.927G>A) is common (popmax 5.97%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.927G>A · rs112332573 · VCV130057

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.97%, afr) — too common for a highly-penetrant pathogenic allele

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP -0.56, phastCons 0.95
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.97% African / African-American · 4,476/75,026 alleles

Filtering AF 5.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.76%

Overall 0.317% 5,117/1,614,024 alleles · common exomes 2,574/1,461,818 · genomes 2,543/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.97%	17
Admixed American	0.417%	240
Remaining individualsnot grpmax-eligible	0.384%	260
Middle Eastern	0.198%	505
South Asian	0.0176%	5,692
European (non-Finnish)	0.0103%	9,752
Finnishnot grpmax-eligible	0.00312%	32,015

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.Ala309=
Coding: c.927G>A
MANE Select: NM_012232
dbSNP: rs112332573
Type: single nucleotide variant
Location: chr17:42404933 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.03 · 3 PDB

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-ala309 (accessed [today's date]).

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