Is EPS8L3 p.Arg442= (c.1326G>A) pathogenic?

EPS8L3 p.Arg442= (c.1326G>A) is classified Likely benign in EPS8L3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 8.47e-05%, nfe).

How common is EPS8L3 p.Arg442= (c.1326G>A) in the general population?

EPS8L3 p.Arg442= (c.1326G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EPS8L3 p.Arg442=

c.1326G>A · rs1426540460 · VCV2638986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -1.2	GERP -0.003
Overall
CADD	2.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 0.000658% 1/152,064 alleles · very rare

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: EPS8L3
Protein: p.Arg442=
Coding: c.1326G>A
MANE Select: NM_133181
dbSNP: rs1426540460
Type: single nucleotide variant
Location: chr1:109752103 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 1 PDB
Residue 442: the 'disordered' region

Full EPS8L3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8L3 p.Leu453Pro Uncertain significance ★★ ⚠ same type
EPS8L3 p.Phe318Leu Uncertain significance ★★ ⚠ same type
EPS8L3 p.Thr36Ile Uncertain significance ★★ ⚠ same type
EPS8L3 p.Asp481= Benign ★★ same type
EPS8L3 p.Ala181Pro Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala215Thr Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala282Val Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala8Thr 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/eps8l3-p-arg442 (accessed [today's date]).

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