Is EFEMP1 p.Asp175= (c.525C>T) pathogenic?

EFEMP1 p.Asp175= (c.525C>T) is classified Conflicting classifications of pathogenicity in EFEMP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-07-25). Very rare (popmax 0.00667%, amr); Associated with Doyne honeycomb retinal dystrophy.

What condition is associated with EFEMP1 p.Asp175= (c.525C>T)?

EFEMP1 p.Asp175= (c.525C>T) is associated with Doyne honeycomb retinal dystrophy (ClinVar).

How common is EFEMP1 p.Asp175= (c.525C>T) in the general population?

EFEMP1 p.Asp175= (c.525C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Familial drusen inherited?

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

EFEMP1 p.Asp175=

c.525C>T · rs151171192 · VCV1942561

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 0.00667%, amr)

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 -0.58	GERP -5.2
Overall
CADD	3.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,966 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00347% 56/1,613,750 alleles · very rare exomes 50/1,461,600 · genomes 6/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00801%	12,490
Admixed Americangrpmax	0.00667%	14,991
European (non-Finnish)	0.00356%	28,092
African / African-American	0.00267%	37,448
South Asian	0.0022%	45,540
Finnishnot grpmax-eligible	0.00156%	64,026

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp175=
Coding: c.525C>T
MANE Select: NM_001039348
dbSNP: rs151171192
Type: single nucleotide variant
Location: chr2:55881727 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 175: the egf-like 2; calcium-binding 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.Asp175Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-asp175 (accessed [today's date]).

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