Is DSCAM p.Pro736Arg (c.2207C>G) pathogenic?

DSCAM p.Pro736Arg (c.2207C>G) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: ambiguous (0.3508); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Pro736Arg (c.2207C>G)?

DSCAM p.Pro736Arg (c.2207C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Pro736Arg (c.2207C>G) in the general population?

DSCAM p.Pro736Arg (c.2207C>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about DSCAM p.Pro736Arg (c.2207C>G)?

AlphaMissense predicts ambiguous (score 0.3508) — an in-silico prediction, not a clinical call.

DSCAM p.Pro736Arg

c.2207C>G · rs1248939413 · VCV3085876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3508	ambiguous
REVEL	0.45	indeterminate
SaProt	LLR -8.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	25.9	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 8.49e-05% European (non-Finnish) · 1/1,177,320 alleles

Overall 6.23e-05% 1/1,606,398 alleles · very rare exomes 1/1,454,164 · genomes 0/152,234 · joint denominator

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.Pro736Arg
Coding: c.2207C>G
MANE Select: NM_001389
dbSNP: rs1248939413
Type: single nucleotide variant
Location: chr21:40276246 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 736: the ig-like c2-type 8 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.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
DSCAM c.5185+2T>A Uncertain significance ★ same condition
DSCAM c.5185+2T>C 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-pro736arg (accessed [today's date]).

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