Is EFEMP1 p.Pro232fs (c.690_693dup) pathogenic?

EFEMP1 p.Pro232fs (c.690693dup) is classified Pathogenic in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Absent from gnomAD.

How common is EFEMP1 p.Pro232fs (c.690_693dup) in the general population?

EFEMP1 p.Pro232fs (c.690_693dup) is absent from gnomAD (gnomAD).

EFEMP1 p.Pro232fs

c.690_693dup · rs2465752553 · VCV2819332

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	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.Pro232fs
Coding: c.690_693dup
MANE Select: NM_001039348
dbSNP: rs2465752553
Type: Duplication
Location: chr2:55877812 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 232: a disulfide bond; a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 3; calcium-binding domain

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

Similar variants

EFEMP1 p.Pro232Arg Uncertain significance ★★ same residue
EFEMP1 p.Pro232Gln Uncertain significance ★ ⚠ same residue
EFEMP1 p.Pro232= Likely benign ★ same residue
EFEMP1 c.1000+10dup Benign/Likely benign ★★ same type
EFEMP1 c.117_130+5dup Uncertain significance ★ same type
EFEMP1 p.Leu5fs Uncertain significance ★ same type
EFEMP1 c.1321-223dup Benign ★ 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-pro232fs (accessed [today's date]).

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