Is EPB41 p.Pro562Ser (c.1684C>T) pathogenic?

EPB41 p.Pro562Ser (c.1684C>T) is classified Uncertain significance in EPB41 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-06). AlphaMissense: ambiguous (0.3961); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EPB41 p.Pro562Ser (c.1684C>T)?

EPB41 p.Pro562Ser (c.1684C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EPB41 p.Pro562Ser (c.1684C>T) in the general population?

EPB41 p.Pro562Ser (c.1684C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPB41 p.Pro562Ser (c.1684C>T)?

AlphaMissense predicts ambiguous (score 0.3961) — an in-silico prediction, not a clinical call.

EPB41 p.Pro562Ser

c.1684C>T · rs2548449288 · VCV2317389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3961	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -10.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 97 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	24.5	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.Pro562Ser
Coding: c.1684C>T
MANE Select: NM_001376013
dbSNP: rs2548449288
Type: single nucleotide variant
Location: chr1:29053151 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.72 · 3 PDB
Residue 562: the 'hydrophilic' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPB41 p.Ala502Val Uncertain significance ★★ ⚠ same condition
EPB41 p.Arg276His Uncertain significance ★★ ⚠ same condition
EPB41 p.Arg815Cys Uncertain significance ★★ ⚠ same condition
EPB41 p.Arg815His Uncertain significance ★★ ⚠ same condition
EPB41 p.Asn244Ser Uncertain significance ★★ ⚠ same condition
EPB41 p.Asp299Gly Uncertain significance ★★ ⚠ same condition
EPB41 p.Asp847Gly Uncertain significance ★★ ⚠ same condition
EPB41 p.Glu677Gly 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-pro562ser (accessed [today's date]).

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