Is EFEMP2 p.Trp15Ter (c.44G>A) pathogenic?

EFEMP2 p.Trp15Ter (c.44G>A) is classified Pathogenic in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). No allele count reported in gnomAD v4.1 (AN 1,551,730); Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Trp15Ter (c.44G>A)?

EFEMP2 p.Trp15Ter (c.44G>A) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Trp15Ter (c.44G>A) in the general population?

EFEMP2 p.Trp15Ter (c.44G>A) is no allele count reported in gnomAD v4.1 (AN 1,551,730) (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.Trp15Ter

c.44G>A · VCV3662053

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,730)

Conditions

cutis laxa, autosomal recessive, type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	Δ0.38	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.2	GERP 0.84, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,551,730). 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.Trp15Ter
Coding: c.44G>A
MANE Select: NM_016938
Type: single nucleotide variant
Location: chr11:65872311 (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 p.Trp15Gly Uncertain significance ★ ⚠ same residue
EFEMP2 p.Arg279Cys Likely pathogenic ★★ same condition
EFEMP2 p.Asp203Ala Pathogenic/Likely pathogenic ★★ same condition
EFEMP2 p.Glu126Lys Pathogenic/Likely pathogenic ★★ same condition
EFEMP2 p.Glu161Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
EFEMP2 p.Glu167Ter Pathogenic ★★ same condition
EFEMP2 c.161-6C>G Uncertain significance ★★ same condition
EFEMP2 c.491-5C>G 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-trp15ter (accessed [today's date]).

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