Is DSCAM p.Arg1220Ter (c.3658C>T) pathogenic?

DSCAM p.Arg1220Ter (c.3658C>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-28). Very rare (popmax 0.000169%, nfe).

How common is DSCAM p.Arg1220Ter (c.3658C>T) in the general population?

DSCAM p.Arg1220Ter (c.3658C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

DSCAM p.Arg1220Ter

c.3658C>T · rs867787586 · VCV1977311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 20 of 33
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,878 alleles · very rare

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.Arg1220Ter
Coding: c.3658C>T
MANE Select: NM_001389
dbSNP: rs867787586
Type: single nucleotide variant
Location: chr21:40124233 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1220: the fibronectin type-iii 4 domain

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

Similar variants

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
DSCAM p.Gln582= 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-arg1220ter (accessed [today's date]).

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