Is DSCAM p.Arg284Cys (c.850C>T) pathogenic?

DSCAM p.Arg284Cys (c.850C>T) is classified Likely benign in DSCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely pathogenic (0.617); Ultra-rare (popmax 0.0188%, sas); Associated with intellectual disability.

What condition is associated with DSCAM p.Arg284Cys (c.850C>T)?

DSCAM p.Arg284Cys (c.850C>T) is associated with intellectual disability (ClinVar).

How common is DSCAM p.Arg284Cys (c.850C>T) in the general population?

DSCAM p.Arg284Cys (c.850C>T) is ultra-rare (popmax 0.0188%, sas) (gnomAD).

What do computational predictors say about DSCAM p.Arg284Cys (c.850C>T)?

AlphaMissense predicts likely pathogenic (score 0.617) — an in-silico prediction, not a clinical call.

DSCAM p.Arg284Cys

c.850C>T · rs267606133 · VCV81855

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.617 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.617	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -10.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.0188% South Asian · 17/90,580 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00981%

Overall 0.0072% 116/1,611,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0188%	5,328
Remaining individualsnot grpmax-eligible	0.00962%	10,398
European (non-Finnish)	0.0078%	12,818
African / African-American	0.00134%	74,776

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSCAM
Protein: p.Arg284Cys
Coding: c.850C>T
MANE Select: NM_001389
dbSNP: rs267606133
Type: single nucleotide variant
Location: chr21:40353549 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 284: a disulfide bond; the ig-like c2-type 3 domain

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

Similar variants

DSCAM p.Arg284His Uncertain significance ★ ⚠ same residue
DSCAM p.Lys936Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Val1788Ile Uncertain significance ★ ⚠ same condition
DSCAM p.Pro1757Thr Likely benign ★ same condition
DSCAM p.Pro446Leu Likely benign ★ ⚠ same condition
DSCAM p.Ile1017Phe Likely benign same condition
DSCAM p.Phe1516Leu Likely benign ⚠ same condition
DSCAM p.Phe909fs 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-arg284cys (accessed [today's date]).

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