Is EFEMP2 p.Cys80Phe (c.239G>T) pathogenic?

EFEMP2 p.Cys80Phe (c.239G>T) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1.

How common is EFEMP2 p.Cys80Phe (c.239G>T) in the general population?

EFEMP2 p.Cys80Phe (c.239G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP2 p.Cys80Phe (c.239G>T)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

EFEMP2 p.Cys80Phe

c.239G>T · VCV4882579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic · top 10% in EFEMP2
REVEL	0.962	strongly pathogenic-leaning
SaProt	LLR -16.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	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	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Cys80Phe
Coding: c.239G>T
MANE Select: NM_016938
Type: single nucleotide variant
Location: chr11:65871285 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 80: a disulfide bond; the egf-like 1; atypical domain; a β-strand

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

Similar variants

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
EFEMP2 c.491-5C>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-cys80phe (accessed [today's date]).

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