Is EFEMP2 p.Ser146del (c.437_439del) pathogenic?

EFEMP2 p.Ser146del (c.437439del) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-12). Absent from gnomAD; Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Ser146del (c.437_439del)?

EFEMP2 p.Ser146del (c.437_439del) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Ser146del (c.437_439del) in the general population?

EFEMP2 p.Ser146del (c.437_439del) is absent from gnomAD (gnomAD).

How is Autosomal recessive cutis laxa type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EFEMP2 p.Ser146del

c.437_439del · rs2134751198 · VCV1059826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cutis laxa, autosomal recessive, type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP -0.34, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EFEMP2
Protein: p.Ser146del
Coding: c.437_439del
MANE Select: NM_016938
dbSNP: rs2134751198
Type: Deletion
Location: chr11:65870587 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 146: a disulfide bond; the egf-like 2; calcium-binding domain

Full EFEMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cutis laxa, autosomal recessive, type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cutis laxa type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

EFEMP2 c.109_111+3del Likely pathogenic ★ same condition
EFEMP2 c.848-1_850del Likely pathogenic ★ same condition
EFEMP2 p.Arg379fs Pathogenic ★ same condition
EFEMP2 p.Gly112_Tyr113insTer Pathogenic ★ same condition
EFEMP2 p.Gly231_Tyr232insTer Pathogenic ★ same condition
EFEMP2 p.Ile392fs Pathogenic ★ same condition
EFEMP2 p.Tyr155fs Pathogenic ★ same condition
EFEMP2 c.111+4_111+12del 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/efemp2-p-ser146del (accessed [today's date]).

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