Is DSCAM p.Leu1084= (c.3252C>T) pathogenic?

DSCAM p.Leu1084= (c.3252C>T) is classified Likely benign in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Ultra-rare (popmax 0.0164%, mid).

How common is DSCAM p.Leu1084= (c.3252C>T) in the general population?

DSCAM p.Leu1084= (c.3252C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

DSCAM p.Leu1084=

c.3252C>T · VCV4533872

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3.6, phastCons 0.062
Overall
CADD	6.872	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.0108% 174/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.138%	722
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0103%	9,671
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.005%	20,003
Finnishnot grpmax-eligible	0.00312%	32,021
African / African-American	0.00133%	74,946

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu1084=
Coding: c.3252C>T
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40144498 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1084: the fibronectin type-iii 2 domain

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-leu1084 (accessed [today's date]).

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