Is DSCAM p.Arg241Cys (c.721C>T) pathogenic?

DSCAM p.Arg241Cys (c.721C>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.8301); Very rare (popmax 0.00666%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Arg241Cys (c.721C>T)?

DSCAM p.Arg241Cys (c.721C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Arg241Cys (c.721C>T) in the general population?

DSCAM p.Arg241Cys (c.721C>T) is very rare (popmax 0.00666%, sas) (gnomAD).

What do computational predictors say about DSCAM p.Arg241Cys (c.721C>T)?

AlphaMissense predicts likely pathogenic (score 0.8301) — an in-silico prediction, not a clinical call.

DSCAM p.Arg241Cys

c.721C>T · VCV4244931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8301	likely pathogenic
REVEL	0.177	moderately benign-leaning
SaProt	LLR -11.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	29.1	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 0.00666% South Asian · 6/90,078 alleles

Filtering AF 0.00289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00197%

Overall 0.000622% 10/1,607,786 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00666%	15,013
Admixed American	0.00172%	58,038
European (non-Finnish)	0.000255%	392,744

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.Arg241Cys
Coding: c.721C>T
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40353678 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 241: 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.Arg241Ser Uncertain significance ★ ⚠ same residue
DSCAM p.Arg241His Uncertain significance ⚠ 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

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-arg241cys (accessed [today's date]).

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