Is DSCAM p.Arg241His (c.722G>A) pathogenic?

DSCAM p.Arg241His (c.722G>A) is classified Uncertain significance in DSCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-26). AlphaMissense: likely benign (0.2122); Very rare (popmax 0.00172%, amr); Associated with DSCAM-related disorder.

What condition is associated with DSCAM p.Arg241His (c.722G>A)?

DSCAM p.Arg241His (c.722G>A) is associated with DSCAM-related disorder (ClinVar).

How common is DSCAM p.Arg241His (c.722G>A) in the general population?

DSCAM p.Arg241His (c.722G>A) is very rare (popmax 0.00172%, amr) (gnomAD).

What do computational predictors say about DSCAM p.Arg241His (c.722G>A)?

AlphaMissense predicts likely benign (score 0.2122) — an in-silico prediction, not a clinical call.

DSCAM p.Arg241His

c.722G>A · rs745604804 · VCV3061576

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DSCAM-related disorder

Computational evidence

Protein change
AlphaMissense	0.2122	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -8.92	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 0.85	GERP -1, phastCons 0.28
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	22.2	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 0.00172% Admixed American · 1/58,154 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000808% 13/1,608,406 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,154
Remaining individualsnot grpmax-eligible	0.00161%	62,216
South Asian	0.00111%	90,194
European (non-Finnish)	0.000849%	117,850

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.Arg241His
Coding: c.722G>A
MANE Select: NM_001389
dbSNP: rs745604804
Type: single nucleotide variant
Location: chr21:40353677 (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

DSCAM-related disorder

Similar variants

DSCAM p.Arg241Cys Uncertain significance ★ ⚠ same residue
DSCAM p.Arg241Ser Uncertain significance ★ ⚠ same residue
DSCAM p.Arg388Leu Uncertain significance ★ ⚠ same condition
DSCAM p.Gly1976Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Lys1283Asn Uncertain significance ★ ⚠ same condition
DSCAM p.Lys391Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Met1548Ile Uncertain significance ★ ⚠ same condition
DSCAM p.Thr485Ile 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-arg241his (accessed [today's date]).

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