Is EFEMP1 p.Ser286Asn (c.857G>A) pathogenic?

EFEMP1 p.Ser286Asn (c.857G>A) is classified Uncertain significance in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: ambiguous (0.5622); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EFEMP1 p.Ser286Asn (c.857G>A)?

EFEMP1 p.Ser286Asn (c.857G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EFEMP1 p.Ser286Asn (c.857G>A) in the general population?

EFEMP1 p.Ser286Asn (c.857G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about EFEMP1 p.Ser286Asn (c.857G>A)?

AlphaMissense predicts ambiguous (score 0.5622) — an in-silico prediction, not a clinical call.

EFEMP1 p.Ser286Asn

c.857G>A · rs1354312053 · VCV3087516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5622	ambiguous
REVEL	0.406	indeterminate
SaProt	LLR -10.99	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 51 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,178,868 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,460,158 alleles · very rare

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.Ser286Asn
Coding: c.857G>A
MANE Select: NM_001039348
dbSNP: rs1354312053
Type: single nucleotide variant
Location: chr2:55876646 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 286: a disulfide bond; a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 4; calcium-binding domain; the 'mediates interaction with timp3' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFEMP1 p.Ala126Pro Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Ala126Thr Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Ala447Thr Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Arg208Gln Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Arg362Gln Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Arg401Gln Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Asn80Ser Uncertain significance ★★ ⚠ same condition
EFEMP1 p.Gln200His Uncertain significance ★★ ⚠ 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-ser286asn (accessed [today's date]).

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