Is EPB41 p.Lys673= (c.2019G>A) pathogenic?

EPB41 p.Lys673= (c.2019G>A) is classified Benign/Likely benign in EPB41 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Low-frequency (popmax 2.4%, afr); Associated with elliptocytosis 1.

What condition is associated with EPB41 p.Lys673= (c.2019G>A)?

EPB41 p.Lys673= (c.2019G>A) is associated with elliptocytosis 1 (ClinVar).

How common is EPB41 p.Lys673= (c.2019G>A) in the general population?

EPB41 p.Lys673= (c.2019G>A) is low-frequency (popmax 2.4%, afr) (gnomAD).

How is Hereditary elliptocytosis inherited?

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

EPB41 p.Lys673=

c.2019G>A · rs79677225 · VCV711837

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.4%, afr)

Conditions

elliptocytosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -4.1, phastCons 1
Overall
CADD	7.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.4% African / African-American · 1,804/75,020 alleles

Filtering AF 2.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.27%

Overall 0.125% 2,023/1,614,004 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.4%	42
Admixed American	0.172%	583
Remaining individualsnot grpmax-eligible	0.155%	644
Middle Eastern	0.0495%	2,021
South Asian	0.00769%	13,009
European (non-Finnish)	0.000763%	131,110

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: EPB41
Protein: p.Lys673=
Coding: c.2019G>A
MANE Select: NM_001376013
dbSNP: rs79677225
Type: single nucleotide variant
Location: chr1:29064993 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 673: the 'spectrin--actin-binding' region

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.Lys673Met Uncertain significance ★ ⚠ same residue
EPB41 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Arg554Ter Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Arg715Ter Pathogenic ★★ same condition
EPB41 p.Gln274Ter Pathogenic ★★ same condition
EPB41 p.Tyr331Ter Pathogenic/Likely pathogenic ★★ same condition
EPB41 p.Ala259Val Uncertain significance ★★ ⚠ same condition
EPB41 p.Ala502Val Uncertain significance ★★ ⚠ 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-lys673 (accessed [today's date]).

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