Is DSCAM p.Val595Leu (c.1783G>C) pathogenic?

DSCAM p.Val595Leu (c.1783G>C) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). AlphaMissense: ambiguous (0.3681); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with DSCAM p.Val595Leu (c.1783G>C)?

DSCAM p.Val595Leu (c.1783G>C) is associated with intellectual disability (ClinVar).

How common is DSCAM p.Val595Leu (c.1783G>C) in the general population?

DSCAM p.Val595Leu (c.1783G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSCAM p.Val595Leu (c.1783G>C)?

AlphaMissense predicts ambiguous (score 0.3681) — an in-silico prediction, not a clinical call.

DSCAM p.Val595Leu

c.1783G>C · rs2074447466 · VCV981301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.3681	ambiguous
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -9.69	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	29.2	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.Val595Leu
Coding: c.1783G>C
dbSNP: rs2074447466
Type: single nucleotide variant
Location: chr21:40338101 (GRCh38)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-val595leu (accessed [today's date]).

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