Is EFEMP2 p.Pro330Arg (c.989C>G) pathogenic?

EFEMP2 p.Pro330Arg (c.989C>G) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-15). AlphaMissense: ambiguous (0.4712); Absent from gnomAD v4.1.

How common is EFEMP2 p.Pro330Arg (c.989C>G) in the general population?

EFEMP2 p.Pro330Arg (c.989C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFEMP2 p.Pro330Arg (c.989C>G)?

AlphaMissense predicts ambiguous (score 0.4712) — an in-silico prediction, not a clinical call.

EFEMP2 p.Pro330Arg

c.989C>G · rs781029572 · VCV1310362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4712	ambiguous
REVEL	0.72	pathogenic-leaning
SaProt	LLR -10.66	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	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	31.0	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.Pro330Arg
Coding: c.989C>G
MANE Select: NM_016938
dbSNP: rs781029572
Type: single nucleotide variant
Location: chr11:65868042 (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

Similar variants

EFEMP2 p.Pro330Leu Uncertain significance ★★ ⚠ same residue
EFEMP2 p.Pro330= Conflicting classifications of pathogenicity ★ 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

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-pro330arg (accessed [today's date]).

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