Is DSCAM p.Ala1742Val (c.5225C>T) pathogenic?

DSCAM p.Ala1742Val (c.5225C>T) is classified Likely benign in DSCAM (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-27). AlphaMissense: likely benign (0.1521); Ultra-rare (popmax 0.0991%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Ala1742Val (c.5225C>T)?

DSCAM p.Ala1742Val (c.5225C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Ala1742Val (c.5225C>T) in the general population?

DSCAM p.Ala1742Val (c.5225C>T) is ultra-rare (popmax 0.0991%, mid) (gnomAD).

What do computational predictors say about DSCAM p.Ala1742Val (c.5225C>T)?

AlphaMissense predicts likely benign (score 0.1521) — an in-silico prediction, not a clinical call.

DSCAM p.Ala1742Val

c.5225C>T · rs191369731 · VCV2394438

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1521 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0991%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1521	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.44	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 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 147 kb · p 2e-13 · regional, not allelic
Overall
CADD	23.7	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 0.0991% Middle Eastern · 6/6,056 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.0139% 225/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0991%	1,009
Admixed American	0.0333%	3,000
Remaining individualsnot grpmax-eligible	0.0192%	5,208
European (non-Finnish)	0.0152%	6,592
South Asian	0.00549%	18,214
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,872
African / African-American	0.00133%	75,054

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.Ala1742Val
Coding: c.5225C>T
MANE Select: NM_001389
dbSNP: rs191369731
Type: single nucleotide variant
Location: chr21:40044236 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1742: the 'required for netrin-mediated axon repulsion of neuronal growth cones' region; the 'disordered' region

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.Ala1742Ser 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
DSCAM c.5185+2T>A 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-ala1742val (accessed [today's date]).

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