Is EFEMP1 p.Leu69= (c.207C>A) pathogenic?

EFEMP1 p.Leu69= (c.207C>A) is classified Benign in EFEMP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 12.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Doyne honeycomb retinal dystrophy.

What condition is associated with EFEMP1 p.Leu69= (c.207C>A)?

EFEMP1 p.Leu69= (c.207C>A) 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.Leu69=

Q: How common is EFEMP1 p.Leu69= (c.207C>A) in the general population?

EFEMP1 p.Leu69= (c.207C>A) is common (popmax 12.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207C>A · rs12292 · VCV336631

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12.2%, afr) — 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.
REVEL	0.066	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.2, phastCons 1
Overall
CADD	7.701	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.2% African / African-American · 9,183/75,020 alleles

Filtering AF 12% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.9%

Overall 0.667% 10,764/1,614,210 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.2%	8
Remaining individualsnot grpmax-eligible	0.88%	114
Admixed American	0.868%	115
Middle Eastern	0.759%	132
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
European (non-Finnish)	0.0346%	2,892
South Asian	0.0231%	4,337

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.Leu69=
Coding: c.207C>A
MANE Select: NM_001039348
dbSNP: rs12292
Type: single nucleotide variant
Location: chr2:55917975 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 69: the egf-like 1; atypical domain

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-leu69 (accessed [today's date]).

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