Is EFEMP1 p.Glu129= (c.387A>G) pathogenic?

EFEMP1 p.Glu129= (c.387A>G) is classified Benign in EFEMP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 8.26%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Doyne honeycomb retinal dystrophy.

What condition is associated with EFEMP1 p.Glu129= (c.387A>G)?

EFEMP1 p.Glu129= (c.387A>G) is associated with Doyne honeycomb retinal dystrophy (ClinVar).

How is Familial drusen inherited?

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

EFEMP1 p.Glu129=

Q: How common is EFEMP1 p.Glu129= (c.387A>G) in the general population?

EFEMP1 p.Glu129= (c.387A>G) is common (popmax 8.26%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.387A>G · rs14282 · VCV93482

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 8.26%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Doyne honeycomb retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 0.18, phastCons 0.8
Overall
CADD	8.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.26% Middle Eastern · 501/6,062 alleles

Filtering AF 7.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.68%

Overall 2.75% 44,404/1,614,206 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	8.26%	12
South Asian	7.9%	13
Ashkenazi Jewishnot grpmax-eligible	6.41%	16
Remaining individualsnot grpmax-eligible	3.24%	31
European (non-Finnish)	2.59%	39
Finnishnot grpmax-eligible	1.67%	60
Admixed American	1.36%	73
Amishnot grpmax-eligible	0.987%	101
African / African-American	0.428%	234
East Asian	0.029%	3,452

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EFEMP1
Protein: p.Glu129=
Coding: c.387A>G
MANE Select: NM_001039348
dbSNP: rs14282
Type: single nucleotide variant
Location: chr2:55917795 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67

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

Disease context

Doyne honeycomb retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial drusen (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

EFEMP1 p.Arg345Trp Pathogenic/Likely pathogenic ★★ same condition
EFEMP1 p.Ala447Ser Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Glu374Gln Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Met130Thr Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Pro373Leu Uncertain significance ★★ ⚠ same condition
EFEMP1 c.1001-14C>T Benign ★★ same condition
EFEMP1 c.518-11G>A Benign ★★ same condition
EFEMP1 c.518-13A>G Benign ★★ 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/efemp1-p-glu129 (accessed [today's date]).

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