Is DSCAM p.Ile1429Val (c.4285A>G) pathogenic?

DSCAM p.Ile1429Val (c.4285A>G) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.1493); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Ile1429Val (c.4285A>G)?

DSCAM p.Ile1429Val (c.4285A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Ile1429Val (c.4285A>G) in the general population?

DSCAM p.Ile1429Val (c.4285A>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DSCAM p.Ile1429Val (c.4285A>G)?

AlphaMissense predicts likely benign (score 0.1493) — an in-silico prediction, not a clinical call.

DSCAM p.Ile1429Val

c.4285A>G · rs555123775 · VCV2242587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1493 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1493	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -7.07	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 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 147 kb · p 2e-13 · regional, not allelic
Overall
CADD	21.7	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 0.00439% South Asian · 4/91,070 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000806% 13/1,613,478 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
East Asian	0.00223%	44,790
Admixed American	0.00167%	59,918
European (non-Finnish)	0.000593%	168,554

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.Ile1429Val
Coding: c.4285A>G
MANE Select: NM_001389
dbSNP: rs555123775
Type: single nucleotide variant
Location: chr21:40080287 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1429: the fibronectin type-iii 5 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-ile1429val (accessed [today's date]).

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