Is EPS8 p.Gln137fs (c.409del) pathogenic?

EPS8 p.Gln137fs (c.409del) is classified Pathogenic in EPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Absent from gnomAD.

How common is EPS8 p.Gln137fs (c.409del) in the general population?

EPS8 p.Gln137fs (c.409del) is absent from gnomAD (gnomAD).

EPS8 p.Gln137fs

c.409del · rs2135847318 · VCV1452443

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 6 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPS8
Protein: p.Gln137fs
Coding: c.409del
MANE Select: NM_004447
dbSNP: rs2135847318
Type: Deletion
Location: chr12:15669494 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB
Residue 137: the ptb domain

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

Similar variants

EPS8 c.1434+14del Benign ★★ same type
EPS8 c.2226-3del Benign/Likely benign ★★ same type
EPS8 p.Glu155fs Pathogenic ★ same type
EPS8 p.Pro601fs 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
EPS8 c.1678-176del 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-gln137fs (accessed [today's date]).

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