Is DSCAM p.Arg826Gln (c.2477G>A) pathogenic?

DSCAM p.Arg826Gln (c.2477G>A) is classified Likely benign in DSCAM (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1009); Rare (popmax 0.242%, sas).

How common is DSCAM p.Arg826Gln (c.2477G>A) in the general population?

DSCAM p.Arg826Gln (c.2477G>A) is rare (popmax 0.242%, sas) (gnomAD).

What do computational predictors say about DSCAM p.Arg826Gln (c.2477G>A)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

DSCAM p.Arg826Gln

c.2477G>A · rs199952049 · VCV2652672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -5.70	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 4.8	GERP 0.77, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 147 kb · p 2e-13 · regional, not allelic
Overall
CADD	28.8	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 0.242% South Asian · 220/91,080 alleles

Filtering AF 0.215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0362% 585/1,614,152 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.242%	414
Middle Eastern	0.0495%	2,021
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Finnishnot grpmax-eligible	0.0266%	3,766
European (non-Finnish)	0.0262%	3,819
Admixed American	0.0117%	8,574
African / African-American	0.004%	25,013

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.Arg826Gln
Coding: c.2477G>A
MANE Select: NM_001389
dbSNP: rs199952049
Type: single nucleotide variant
Location: chr21:40189118 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 826: the ig-like c2-type 9 domain; a disulfide bond

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-arg826gln (accessed [today's date]).

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