Is DSCAM p.Arg284His (c.851G>A) pathogenic?

DSCAM p.Arg284His (c.851G>A) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1517); Ultra-rare (popmax 0.0991%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Arg284His (c.851G>A)?

DSCAM p.Arg284His (c.851G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Arg284His (c.851G>A) in the general population?

DSCAM p.Arg284His (c.851G>A) is ultra-rare (popmax 0.0991%, mid) (gnomAD).

What do computational predictors say about DSCAM p.Arg284His (c.851G>A)?

AlphaMissense predicts likely benign (score 0.1517) — an in-silico prediction, not a clinical call.

DSCAM p.Arg284His

c.851G>A · rs140655651 · VCV2378580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1517 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0991%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1517	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0991% Middle Eastern · 6/6,052 alleles

Filtering AF 0.0432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.00838% 135/1,611,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0991%	1,009
South Asian	0.0475%	2,106
East Asian	0.0246%	4,070
Remaining individualsnot grpmax-eligible	0.016%	6,241
African / African-American	0.00801%	12,481
European (non-Finnish)	0.00475%	21,058
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,532
Admixed American	0.00337%	29,671

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.Arg284His
Coding: c.851G>A
MANE Select: NM_001389
dbSNP: rs140655651
Type: single nucleotide variant
Location: chr21:40353548 (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

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

Similar variants

DSCAM p.Arg284Cys Likely benign same residue
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

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-arg284his (accessed [today's date]).

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