Is DSCAM p.Pro220Arg (c.659C>G) pathogenic?

DSCAM p.Pro220Arg (c.659C>G) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.3055); Very rare (popmax 0.00382%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Pro220Arg (c.659C>G)?

DSCAM p.Pro220Arg (c.659C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Pro220Arg (c.659C>G) in the general population?

DSCAM p.Pro220Arg (c.659C>G) is very rare (popmax 0.00382%, nfe) (gnomAD).

What do computational predictors say about DSCAM p.Pro220Arg (c.659C>G)?

AlphaMissense predicts likely benign (score 0.3055) — an in-silico prediction, not a clinical call.

DSCAM p.Pro220Arg

c.659C>G · VCV3505344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00382%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3055	likely benign
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -7.22	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	25.0	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 0.00382% European (non-Finnish) · 44/1,151,652 alleles

Filtering AF 0.0029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00258%

Overall 0.00292% 45/1,540,410 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00382%	26,174
Remaining individualsnot grpmax-eligible	0.00168%	59,448

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.Pro220Arg
Coding: c.659C>G
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40353740 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB

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-pro220arg (accessed [today's date]).

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