Is EPB41 p.Met210Arg (c.629T>G) pathogenic?

EPB41 p.Met210Arg (c.629T>G) is classified Pathogenic in EPB41 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1992-11-01). AlphaMissense: likely pathogenic (0.712); Absent from gnomAD v4.1; Associated with elliptocytosis 1.

What condition is associated with EPB41 p.Met210Arg (c.629T>G)?

EPB41 p.Met210Arg (c.629T>G) is associated with elliptocytosis 1 (ClinVar).

How common is EPB41 p.Met210Arg (c.629T>G) in the general population?

EPB41 p.Met210Arg (c.629T>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary elliptocytosis inherited?

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

What do computational predictors say about EPB41 p.Met210Arg (c.629T>G)?

AlphaMissense predicts likely pathogenic (score 0.712) — an in-silico prediction, not a clinical call.

EPB41 p.Met210Arg

c.629T>G · rs121434564 · VCV16714

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

elliptocytosis 1

Computational evidence

Protein change
AlphaMissense	0.712	likely pathogenic ✓ concordant with ClinVar
REVEL	0.66	pathogenic-leaning
SaProt	LLR -14.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 31 kb · p 0.042 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPB41
Protein: p.Met210Arg
Coding: c.629T>G
MANE Select: NM_001376013
dbSNP: rs121434564
Type: single nucleotide variant
Location: chr1:28993490 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 210: 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.Met210Thr Pathogenic same residue
EPB41 p.Met210Val Pathogenic/Likely pathogenic ★★ ⚠ 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

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-met210arg (accessed [today's date]).

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