Is CAVIN1 p.Val86Met (c.256G>A) pathogenic?

CAVIN1 p.Val86Met (c.256G>A) is classified Uncertain significance in CAVIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-10). AlphaMissense: likely pathogenic (0.6671); Very rare (popmax 0.0033%, sas); Associated with congenital generalized lipodystrophy type 4.

What condition is associated with CAVIN1 p.Val86Met (c.256G>A)?

CAVIN1 p.Val86Met (c.256G>A) is associated with congenital generalized lipodystrophy type 4 (ClinVar).

How common is CAVIN1 p.Val86Met (c.256G>A) in the general population?

CAVIN1 p.Val86Met (c.256G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about CAVIN1 p.Val86Met (c.256G>A)?

AlphaMissense predicts likely pathogenic (score 0.6671) — an in-silico prediction, not a clinical call.

CAVIN1 p.Val86Met

c.256G>A · rs1330090952 · VCV2435297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital generalized lipodystrophy type 4

Computational evidence

Protein change
AlphaMissense	0.6671	likely pathogenic
REVEL	0.269	benign-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 18 kb · p 0.076 · regional, not allelic
Overall
CADD	33.0	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 0.0033% South Asian · 3/91,046 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00093% 15/1,613,676 alleles · very rare exomes 14/1,461,450 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,349
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000932%	107,268

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.Val86Met
Coding: c.256G>A
MANE Select: NM_012232
dbSNP: rs1330090952
Type: single nucleotide variant
Location: chr17:42422842 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.03 · 3 PDB
Residue 86: the 'required for homotrimerization and for interaction with cavin2 and cavin3' region; an α-helix

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-val86met (accessed [today's date]).

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