Is EPB41 p.Arg444fs (c.1330dup) pathogenic?

EPB41 p.Arg444fs (c.1330dup) is classified Likely pathogenic in EPB41 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). Absent from gnomAD; Associated with elliptocytosis 1.

What condition is associated with EPB41 p.Arg444fs (c.1330dup)?

EPB41 p.Arg444fs (c.1330dup) is associated with elliptocytosis 1 (ClinVar).

How common is EPB41 p.Arg444fs (c.1330dup) in the general population?

EPB41 p.Arg444fs (c.1330dup) is absent from gnomAD (gnomAD).

How is Hereditary elliptocytosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EPB41 p.Arg444fs

c.1330dup · rs2548140072 · VCV2440049

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

elliptocytosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 0.43, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPB41
Protein: p.Arg444fs
Coding: c.1330dup
MANE Select: NM_001376013
dbSNP: rs2548140072
Type: Duplication
Location: chr1:29033209 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 444: the ferm domain

Full EPB41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

elliptocytosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary elliptocytosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

EPB41 p.Arg444His Conflicting classifications of pathogenicity ★ ⚠ same residue
EPB41 p.Thr582fs Likely pathogenic ★★ same condition
EPB41 c.829+2dup Uncertain significance ★ same condition
EPB41 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Arg554Ter Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Arg651fs Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Arg715Ter Pathogenic ★★ same condition
EPB41 p.Gln274Ter Pathogenic ★★ 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/epb41-p-arg444fs (accessed [today's date]).

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