Is CAVIN1 p.Val119Asp (c.356T>A) pathogenic?

CAVIN1 p.Val119Asp (c.356T>A) is classified Conflicting classifications of pathogenicity in CAVIN1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-06-01). AlphaMissense: likely pathogenic (0.9124); Rare (popmax 0.334%, nfe); Associated with congenital generalized lipodystrophy type 4.

What condition is associated with CAVIN1 p.Val119Asp (c.356T>A)?

CAVIN1 p.Val119Asp (c.356T>A) is associated with congenital generalized lipodystrophy type 4 (ClinVar).

How common is CAVIN1 p.Val119Asp (c.356T>A) in the general population?

CAVIN1 p.Val119Asp (c.356T>A) is rare (popmax 0.334%, nfe) (gnomAD).

What do computational predictors say about CAVIN1 p.Val119Asp (c.356T>A)?

AlphaMissense predicts likely pathogenic (score 0.9124) — an in-silico prediction, not a clinical call.

CAVIN1 p.Val119Asp

c.356T>A · rs146547678 · VCV193361

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.9124 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.334%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital generalized lipodystrophy type 4

Computational evidence

Protein change
AlphaMissense	0.9124	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -8.52	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 6	GERP -3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 18 kb · p 0.076 · regional, not allelic
Overall
CADD	28.7	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 0.334% European (non-Finnish) · 3,942/1,179,130 alleles

Filtering AF 0.326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.322%

Overall 0.28% 4,515/1,611,682 alleles · rare exomes 4,213/1,459,434 · genomes 302/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.365%	274
European (non-Finnish)grpmax	0.334%	299
Remaining individualsnot grpmax-eligible	0.264%	378
Ashkenazi Jewishnot grpmax-eligible	0.156%	642
Admixed American	0.134%	746
Middle Eastern	0.0826%	1,211
African / African-American	0.0534%	1,874
South Asian	0.00552%	18,131

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val119Asp
Coding: c.356T>A
MANE Select: NM_012232
dbSNP: rs146547678
Type: single nucleotide variant
Location: chr17:42422742 (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-val119asp (accessed [today's date]).

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