Is EPS8 p.Pro601fs (c.1802_1817del) pathogenic?

EPS8 p.Pro601fs (c.18021817del) is classified Pathogenic in EPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). Very rare (popmax 8.48e-05%, nfe).

How common is EPS8 p.Pro601fs (c.1802_1817del) in the general population?

EPS8 p.Pro601fs (c.1802_1817del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

EPS8 p.Pro601fs

c.1802_1817del · rs1565473322 · VCV2127162

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.25	GERP -1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,592 alleles

Overall 6.2e-05% 1/1,613,638 alleles · very rare exomes 1/1,461,318 · genomes 0/152,320 · joint denominator

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: EPS8
Protein: p.Pro601fs
Coding: c.1802_1817del
MANE Select: NM_004447
dbSNP: rs1565473322
Type: Deletion
Location: chr12:15640707 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB

Full EPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8 p.Pro601Thr Uncertain significance ★ ⚠ same residue
EPS8 c.1434+14del Benign ★★ same type
EPS8 c.2226-3del Benign/Likely benign ★★ same type
EPS8 p.Gln137fs Pathogenic ★ same type
EPS8 p.Glu155fs Pathogenic ★ same type
EPS8 c.2225+4_2225+5del Uncertain significance ★ same type
EPS8 c.1250+119del Likely benign ★ same type
EPS8 c.1250+19_1250+28del Likely benign ★ 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/eps8-p-pro601fs (accessed [today's date]).

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