Is DSCAM p.Pro597Leu (c.1790C>T) pathogenic?

DSCAM p.Pro597Leu (c.1790C>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.8228); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Pro597Leu (c.1790C>T)?

DSCAM p.Pro597Leu (c.1790C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Pro597Leu (c.1790C>T) in the general population?

DSCAM p.Pro597Leu (c.1790C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSCAM p.Pro597Leu (c.1790C>T)?

AlphaMissense predicts likely pathogenic (score 0.8228) — an in-silico prediction, not a clinical call.

DSCAM p.Pro597Leu

c.1790C>T · VCV4244950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8228 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8228	likely pathogenic
REVEL	0.759	pathogenic-leaning
SaProt	LLR -11.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro597Leu
Coding: c.1790C>T
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40312353 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 597: the ig-like c2-type 7 domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSCAM p.Ser682Arg Uncertain significance ★★ ⚠ same condition
DSCAM p.Gly1960Glu Likely benign ★★ same condition
DSCAM p.Val757Leu Likely benign ★★ same condition
DSCAM p.Arg1754Ter Pathogenic ★ same condition
DSCAM c.3850+4G>C Uncertain significance ★ same condition
DSCAM c.4889-4C>G Uncertain significance ★ same condition
DSCAM c.5185+2T>A Uncertain significance ★ same condition
DSCAM c.5185+2T>C 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-pro597leu (accessed [today's date]).

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