Is EFEMP1 p.Arg362Ter (c.1084C>T) pathogenic?

EFEMP1 p.Arg362Ter (c.1084C>T) is classified Likely pathogenic in EFEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-03). Very rare (popmax 0.00017%, nfe); Associated with EFEMP1-related connective tissue condition.

What condition is associated with EFEMP1 p.Arg362Ter (c.1084C>T)?

EFEMP1 p.Arg362Ter (c.1084C>T) is associated with EFEMP1-related connective tissue condition (ClinVar).

How common is EFEMP1 p.Arg362Ter (c.1084C>T) in the general population?

EFEMP1 p.Arg362Ter (c.1084C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

EFEMP1 p.Arg362Ter

c.1084C>T · VCV3384188

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

EFEMP1-related connective tissue condition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	Δ0.25	donor loss, 40 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 0.65, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,802 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,616 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EFEMP1
Protein: p.Arg362Ter
Coding: c.1084C>T
MANE Select: NM_001039348
Type: single nucleotide variant
Location: chr2:55871040 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.67
Residue 362: a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 6; calcium-binding domain; the 'mediates interaction with timp3' region

Full EFEMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EFEMP1-related connective tissue condition

Similar variants

EFEMP1 p.Arg362Gln Uncertain significance ★★ ⚠ same residue
EFEMP1 p.Arg345Trp Pathogenic/Likely pathogenic ★★ same condition
EFEMP1 p.Arg140Trp Conflicting classifications of pathogenicity ★ same condition
EFEMP1 p.Asp296fs Pathogenic/Likely pathogenic ★★ same condition
EFEMP1 p.Ala104Thr Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala126Pro Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala126Thr Uncertain significance ★★ ⚠ same type
EFEMP1 p.Ala447Ser 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/efemp1-p-arg362ter (accessed [today's date]).

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