Is EFEMP1 p.Tyr65= (c.195T>C) pathogenic?

EFEMP1 p.Tyr65= (c.195T>C) is classified Conflicting classifications of pathogenicity in EFEMP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-02-13). Very rare (popmax 0.0033%, nfe); Associated with Doyne honeycomb retinal dystrophy.

What condition is associated with EFEMP1 p.Tyr65= (c.195T>C)?

EFEMP1 p.Tyr65= (c.195T>C) is associated with Doyne honeycomb retinal dystrophy (ClinVar).

How common is EFEMP1 p.Tyr65= (c.195T>C) in the general population?

EFEMP1 p.Tyr65= (c.195T>C) is very rare (popmax 0.0033%, nfe) (gnomAD).

How is Familial drusen inherited?

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

EFEMP1 p.Tyr65=

c.195T>C · rs142572513 · VCV896672

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0033%, nfe)

Conditions

Doyne honeycomb retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.153	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -3.5, phastCons 0.005
Overall
CADD	3.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% European (non-Finnish) · 39/1,180,042 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00274% 40/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0033%	30,257
African / African-American	0.00133%	75,060

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.Tyr65=
Coding: c.195T>C
MANE Select: NM_001039348
dbSNP: rs142572513
Type: single nucleotide variant
Location: chr2:55917987 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 65: 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-tyr65 (accessed [today's date]).

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