Is DSCAM p.Tyr397fs (c.1190_1191del) pathogenic?

DSCAM p.Tyr397fs (c.11901191del) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-16).

DSCAM p.Tyr397fs

c.1190_1191del · VCV4946288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: DSCAM
Protein: p.Tyr397fs
Coding: c.1190_1191del
MANE Select: NM_001389
Type: Deletion
Location: chr21:40347689 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 397: the ig-like c2-type 4 domain

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

Similar variants

DSCAM p.Glu1093fs Pathogenic ★ same type
DSCAM p.Phe1206fs Pathogenic ★ same type
DSCAM p.Val618fs Pathogenic ★ same type
DSCAM c.(5035+1_5036-1 Uncertain significance ★ same type
DSCAM c.934+1del Uncertain significance ★ same type
DSCAM p.Phe909fs Uncertain significance ★ same type
DSCAM p.Pro1074fs Uncertain significance ★ same type
DSCAM p.Pro605fs 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/dscam-p-tyr397fs (accessed [today's date]).

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