Is EFEMP2 p.Val395Ala (c.1184T>C) pathogenic?

EFEMP2 p.Val395Ala (c.1184T>C) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). AlphaMissense: ambiguous (0.522); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EFEMP2 p.Val395Ala (c.1184T>C)?

EFEMP2 p.Val395Ala (c.1184T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is EFEMP2 p.Val395Ala (c.1184T>C) in the general population?

EFEMP2 p.Val395Ala (c.1184T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP2 p.Val395Ala (c.1184T>C)?

AlphaMissense predicts ambiguous (score 0.522) — an in-silico prediction, not a clinical call.

EFEMP2 p.Val395Ala

c.1184T>C · rs2495570109 · VCV2312769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.522	ambiguous
REVEL	0.269	benign-leaning
SaProt	LLR -6.01	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 5,433 bp · p 3.8e-05 · regional, not allelic
Overall
CADD	23.4	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

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.Val395Ala
Coding: c.1184T>C
MANE Select: NM_016938
dbSNP: rs2495570109
Type: single nucleotide variant
Location: chr11:65867066 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFEMP2 p.Val395Ile Uncertain significance ★★ ⚠ same residue
EFEMP2 p.Val395Leu Uncertain significance ★ ⚠ same residue
EFEMP2 p.Glu167Ter Pathogenic ★★ same condition
EFEMP2 c.608-3C>G Uncertain significance ★★ same condition
EFEMP2 p.Ala103Thr Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala291Gly Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala85Thr Uncertain significance ★★ ⚠ same condition
EFEMP2 p.Ala86Thr 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/efemp2-p-val395ala (accessed [today's date]).

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