Is EFEMP2 p.Ala130Asp (c.389C>A) pathogenic?

EFEMP2 p.Ala130Asp (c.389C>A) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.0591); Absent from gnomAD v4.1.

How common is EFEMP2 p.Ala130Asp (c.389C>A) in the general population?

EFEMP2 p.Ala130Asp (c.389C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP2 p.Ala130Asp (c.389C>A)?

AlphaMissense predicts likely benign (score 0.0591) — an in-silico prediction, not a clinical call.

EFEMP2 p.Ala130Asp

c.389C>A · VCV3377947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0591	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.74	GERP -3.7, phastCons 0.63
Regional constraint	o/e 0.83	unconstrained · MANE · 5,433 bp · p 3.8e-05 · regional, not allelic
Overall
CADD	8.336	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFEMP2
Protein: p.Ala130Asp
Coding: c.389C>A
MANE Select: NM_016938
Type: single nucleotide variant
Location: chr11:65870637 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 130: the egf-like 2; calcium-binding domain

Full EFEMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFEMP2 p.Ala130= Likely benign ★ same residue
EFEMP2 p.Arg279Cys Likely pathogenic ★★ same type
EFEMP2 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same type
EFEMP2 p.Asp203Ala Pathogenic/Likely pathogenic ★★ same type
EFEMP2 p.Glu126Lys Pathogenic/Likely pathogenic ★★ same type
EFEMP2 p.Glu161Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
EFEMP2 p.Glu167Ter Pathogenic ★★ same type
EFEMP2 c.161-6C>G Uncertain significance ★★ same type

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/efemp2-p-ala130asp (accessed [today's date]).

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