Is EPB42 p.Arg336Pro (c.1007G>C) pathogenic?

EPB42 p.Arg336Pro (c.1007G>C) is classified Uncertain significance in EPB42 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: ambiguous (0.4957); Absent from gnomAD v4.1.

How common is EPB42 p.Arg336Pro (c.1007G>C) in the general population?

EPB42 p.Arg336Pro (c.1007G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPB42 p.Arg336Pro (c.1007G>C)?

AlphaMissense predicts ambiguous (score 0.4957) — an in-silico prediction, not a clinical call.

EPB42 p.Arg336Pro

c.1007G>C · VCV3772490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4957	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -13.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 0.054, phastCons 0.77
Regional constraint	o/e 0.84	unconstrained · MANE · 24 kb · p 3.5e-06 · regional, not allelic
Overall
CADD	23.5	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: EPB42
Protein: p.Arg336Pro
Coding: c.1007G>C
MANE Select: NM_001114134
Type: single nucleotide variant
Location: chr15:43208298 (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

Similar variants

EPB42 p.Arg336Gln Uncertain significance ★★ ⚠ same residue
EPB42 p.Arg336Trp Uncertain significance ★ ⚠ same residue
EPB42 p.Arg259Ter Pathogenic/Likely pathogenic ★★ same type
EPB42 p.Arg310Gln Likely pathogenic ★★ same type
EPB42 c.10+51G>A Uncertain significance ★★ same type
EPB42 p.Ala353Val Uncertain significance ★★ ⚠ same type
EPB42 p.Ala51Thr Uncertain significance ★★ ⚠ same type
EPB42 p.Ala566Thr Uncertain significance ★★ ⚠ same type

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-arg336pro (accessed [today's date]).

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