Is DSCAM p.Asp445Val (c.1334A>T) pathogenic?

DSCAM p.Asp445Val (c.1334A>T) is classified Uncertain significance in DSCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-22). AlphaMissense: ambiguous (0.3654); Absent from gnomAD v4.1; Associated with DSCAM-related disorder.

What condition is associated with DSCAM p.Asp445Val (c.1334A>T)?

DSCAM p.Asp445Val (c.1334A>T) is associated with DSCAM-related disorder (ClinVar).

How common is DSCAM p.Asp445Val (c.1334A>T) in the general population?

DSCAM p.Asp445Val (c.1334A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSCAM p.Asp445Val (c.1334A>T)?

AlphaMissense predicts ambiguous (score 0.3654) — an in-silico prediction, not a clinical call.

DSCAM p.Asp445Val

c.1334A>T · VCV3350201

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3654 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DSCAM-related disorder

Computational evidence

Protein change
AlphaMissense	0.3654	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -6.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	24.6	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: DSCAM
Protein: p.Asp445Val
Coding: c.1334A>T
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40339292 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 445: a disulfide bond; the ig-like c2-type 5 domain

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

Disease context

DSCAM-related disorder

Similar variants

DSCAM p.Arg388Leu Uncertain significance ★ ⚠ same condition
DSCAM p.Gly1976Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Lys1283Asn Uncertain significance ★ ⚠ same condition
DSCAM p.Lys391Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Met1548Ile Uncertain significance ★ ⚠ same condition
DSCAM p.Thr485Ile Uncertain significance ★ ⚠ same condition
DSCAM c.5036-2A>G Uncertain significance same condition
DSCAM p.Arg1657Ter Uncertain significance same condition

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-asp445val (accessed [today's date]).

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