Is EPB42 p.Ala110= (c.330G>A) pathogenic?

EPB42 p.Ala110= (c.330G>A) is classified Benign in EPB42 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Common (popmax 12.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spherocytosis type 5.

What condition is associated with EPB42 p.Ala110= (c.330G>A)?

EPB42 p.Ala110= (c.330G>A) is associated with hereditary spherocytosis type 5 (ClinVar).

How is Hereditary spherocytosis inherited?

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

EPB42 p.Ala110=

Q: How common is EPB42 p.Ala110= (c.330G>A) in the general population?

EPB42 p.Ala110= (c.330G>A) is common (popmax 12.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330G>A · rs1042168 · VCV255153

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 12.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spherocytosis type 5

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 -3	GERP -4.6
Overall
CADD	10.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.2% African / African-American · 9,157/75,012 alleles

Filtering AF 12% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.9%

Overall 0.77% 12,430/1,614,172 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.2%	8
East Asian	2.77%	36
Remaining individualsnot grpmax-eligible	1.39%	72
Middle Eastern	0.742%	135
Admixed American	0.721%	139
South Asian	0.345%	290
Ashkenazi Jewishnot grpmax-eligible	0.209%	478
European (non-Finnish)	0.026%	3,844

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: EPB42
Protein: p.Ala110=
Coding: c.330G>A
MANE Select: NM_001114134
dbSNP: rs1042168
Type: single nucleotide variant
Location: chr15:43215195 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.35 · 13 PDB

Full EPB42 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spherocytosis type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary spherocytosis (Orphanet):

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

Similar variants

EPB42 p.Ala110Val Uncertain significance ★ ⚠ same residue
EPB42 p.Arg259Ter Pathogenic/Likely pathogenic ★★ same condition
EPB42 p.Arg310Gln Likely pathogenic ★★ ⚠ same condition
EPB42 c.10+51G>A Uncertain significance ★★ same condition
EPB42 p.Ala353Val Uncertain significance ★★ ⚠ same condition
EPB42 p.Ala51Thr Uncertain significance ★★ ⚠ same condition
EPB42 p.Ala566Thr Uncertain significance ★★ ⚠ same condition
EPB42 p.Arg155Cys 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/epb42-p-ala110 (accessed [today's date]).

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