Is EFEMP2 p.Val395Phe (c.1183G>T) pathogenic?

EFEMP2 p.Val395Phe (c.1183G>T) is classified Uncertain significance in EFEMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-27). AlphaMissense: likely benign (0.3072); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EFEMP2 p.Val395Phe (c.1183G>T)?

EFEMP2 p.Val395Phe (c.1183G>T) is associated with Cardiovascular phenotype, cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Val395Phe (c.1183G>T) in the general population?

EFEMP2 p.Val395Phe (c.1183G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP2 p.Val395Phe (c.1183G>T)?

AlphaMissense predicts likely benign (score 0.3072) — an in-silico prediction, not a clinical call.

EFEMP2 p.Val395Phe

c.1183G>T · rs543567156 · VCV1742839

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3072 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3072	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.5	GERP 0.73, phastCons 0.99
Regional constraint	o/e 0.83	unconstrained · MANE · 5,433 bp · p 3.8e-05 · regional, not allelic
Overall
CADD	25.5	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.Val395Phe
Coding: c.1183G>T
MANE Select: NM_025128 · reported on NM_016938
dbSNP: rs543567156
Type: single nucleotide variant
Location: chr11:65867067 (GRCh38)

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

Also linked: cutis laxa, autosomal recessive, type 1B

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-val395phe (accessed [today's date]).

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