Is DSCAM p.Arg1657Gln (c.4970G>A) pathogenic?

DSCAM p.Arg1657Gln (c.4970G>A) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). AlphaMissense: likely benign (0.1873); Ultra-rare (popmax 0.0267%, amr).

How common is DSCAM p.Arg1657Gln (c.4970G>A) in the general population?

DSCAM p.Arg1657Gln (c.4970G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about DSCAM p.Arg1657Gln (c.4970G>A)?

AlphaMissense predicts likely benign (score 0.1873) — an in-silico prediction, not a clinical call.

DSCAM p.Arg1657Gln

c.4970G>A · rs766747740 · VCV3239305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1873	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -5.46	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 147 kb · p 2e-13 · regional, not allelic
Overall
CADD	26.7	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 0.0267% Admixed American · 16/59,986 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00155% 25/1,613,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,749
African / African-American	0.00133%	74,920
South Asian	0.0011%	91,072
European (non-Finnish)	0.000593%	168,546

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.Arg1657Gln
Coding: c.4970G>A
MANE Select: NM_001389
dbSNP: rs766747740
Type: single nucleotide variant
Location: chr21:40055790 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1657: the 'required for netrin-mediated axon repulsion of neuronal growth cones' region

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

Similar variants

DSCAM p.Arg1657Ter Uncertain significance same residue
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

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-arg1657gln (accessed [today's date]).

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