Is EPB41 p.Asp600= (c.1800C>T) pathogenic?

EPB41 p.Asp600= (c.1800C>T) is classified Likely benign in EPB41 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-17). Rare (popmax 0.528%, mid); Associated with elliptocytosis 1.

What condition is associated with EPB41 p.Asp600= (c.1800C>T)?

EPB41 p.Asp600= (c.1800C>T) is associated with elliptocytosis 1 (ClinVar).

How common is EPB41 p.Asp600= (c.1800C>T) in the general population?

EPB41 p.Asp600= (c.1800C>T) is rare (popmax 0.528%, mid) (gnomAD).

How is Hereditary elliptocytosis inherited?

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

EPB41 p.Asp600=

c.1800C>T · rs139530083 · VCV2052068

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.528%, mid)

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 0.56	GERP -5.1, phastCons 0.045
Overall
CADD	9.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.528% Middle Eastern · 32/6,062 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0183% 295/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.528%	189
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.0285%	3,503
European (non-Finnish)	0.0175%	5,728
African / African-American	0.00533%	18,758
Admixed American	0.005%	19,994
East Asian	0.00446%	22,442
Finnishnot grpmax-eligible	0.00312%	32,009

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.Asp600=
Coding: c.1800C>T
MANE Select: NM_001376013
dbSNP: rs139530083
Type: single nucleotide variant
Location: chr1:29053267 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 600: the 'hydrophilic' region; the 'disordered' 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.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
EPB41 p.Ala535Val 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-asp600 (accessed [today's date]).

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