Is EFEMP1 p.Asp296fs (c.888del) pathogenic?

EFEMP1 p.Asp296fs (c.888del) is classified Pathogenic/Likely pathogenic in EFEMP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-02). Absent from gnomAD; Associated with EFEMP1-related disorder.

What condition is associated with EFEMP1 p.Asp296fs (c.888del)?

EFEMP1 p.Asp296fs (c.888del) is associated with EFEMP1-related disorder (ClinVar).

How common is EFEMP1 p.Asp296fs (c.888del) in the general population?

EFEMP1 p.Asp296fs (c.888del) is absent from gnomAD (gnomAD).

EFEMP1 p.Asp296fs

c.888del · rs2465744658 · VCV2635191

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

EFEMP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1

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

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: EFEMP1
Protein: p.Asp296fs
Coding: c.888del
MANE Select: NM_001039348
dbSNP: rs2465744658
Type: Deletion
Location: chr2:55875058 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 296: a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 5; calcium-binding domain; the 'mediates interaction with timp3' region

Full EFEMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFEMP1-related disorder

Similar variants

EFEMP1 p.Arg345Trp Pathogenic/Likely pathogenic ★★ same condition
EFEMP1 p.Arg362Ter Likely pathogenic ★ same condition
EFEMP1 p.Arg140Trp Conflicting classifications of pathogenicity ★ same condition
EFEMP1 c.1000+19del Benign ★★ same type
EFEMP1 c.*6del Benign/Likely benign ★★ same type
EFEMP1 p.Asp53fs Pathogenic ★ same type
EFEMP1 p.Met107fs Pathogenic ★ same type
EFEMP1 c.761-26_761-13del Uncertain significance ★ same type

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/efemp1-p-asp296fs (accessed [today's date]).

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