Is DSCAM p.Arg635Trp (c.1903C>T) pathogenic?

DSCAM p.Arg635Trp (c.1903C>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-03). AlphaMissense: likely benign (0.2844); Ultra-rare (popmax 0.0575%, nfe).

How common is DSCAM p.Arg635Trp (c.1903C>T) in the general population?

DSCAM p.Arg635Trp (c.1903C>T) is ultra-rare (popmax 0.0575%, nfe) (gnomAD).

What do computational predictors say about DSCAM p.Arg635Trp (c.1903C>T)?

AlphaMissense predicts likely benign (score 0.2844) — an in-silico prediction, not a clinical call.

DSCAM p.Arg635Trp

c.1903C>T · VCV4886193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2844 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0575%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2844	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -11.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	29.7	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 0.0575% European (non-Finnish) · 679/1,180,018 alleles

Filtering AF 0.0539% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0525%

Overall 0.0462% 745/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0575%	1,738
Remaining individualsnot grpmax-eligible	0.0544%	1,837
Finnishnot grpmax-eligible	0.0234%	4,268
Admixed American	0.015%	6,666
African / African-American	0.0107%	9,362

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.Arg635Trp
Coding: c.1903C>T
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40312240 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 635: the ig-like c2-type 7 domain; a disulfide bond

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

Similar variants

DSCAM p.Arg635Gln Uncertain significance ★ ⚠ same residue
DSCAM p.Ser682Arg Uncertain significance ★★ ⚠ same type
DSCAM c.5383+9T>A Benign ★★ same type
DSCAM p.Ala153= Benign ★★ same type
DSCAM p.Arg1798= Benign/Likely benign ★★ same type
DSCAM p.Asn1250= Benign ★★ same type
DSCAM p.Asn576= Benign/Likely benign ★★ same type
DSCAM p.Asp185= Benign/Likely benign ★★ same type

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-arg635trp (accessed [today's date]).

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