Is EFEMP2 p.Arg379fs (c.1135del) pathogenic?

EFEMP2 p.Arg379fs (c.1135del) is classified Pathogenic in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Arg379fs (c.1135del)?

EFEMP2 p.Arg379fs (c.1135del) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

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.Arg379fs

c.1135del · VCV3653395

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

cutis laxa, autosomal recessive, type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (10 of 11, 35 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP -0.45, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EFEMP2
Protein: p.Arg379fs
Coding: c.1135del
MANE Select: NM_016938
Type: Deletion
Location: chr11:65867896 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB

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.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
EFEMP2 p.Asn260del 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-arg379fs (accessed [today's date]).

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