Is DSCAM p.Thr62= (c.186G>A) pathogenic?

DSCAM p.Thr62= (c.186G>A) is classified Likely benign in DSCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-25). Very rare (popmax 0.00267%, afr); Associated with DSCAM-related disorder.

What condition is associated with DSCAM p.Thr62= (c.186G>A)?

DSCAM p.Thr62= (c.186G>A) is associated with DSCAM-related disorder (ClinVar).

How common is DSCAM p.Thr62= (c.186G>A) in the general population?

DSCAM p.Thr62= (c.186G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

DSCAM p.Thr62=

c.186G>A · rs754899814 · VCV3057009

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

DSCAM-related disorder

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 0.43	GERP -2.4, phastCons 0.99
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000868% 14/1,612,850 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,460
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000933%	107,229

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.Thr62=
Coding: c.186G>A
MANE Select: NM_001389
dbSNP: rs754899814
Type: single nucleotide variant
Location: chr21:40708629 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 62: a disulfide bond; the ig-like c2-type 1 domain

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

Disease context

DSCAM-related disorder

Similar variants

DSCAM p.Thr62Met Likely benign ⚠ same residue
DSCAM p.Arg388Leu Uncertain significance ★ ⚠ same condition
DSCAM p.Gly1976Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Lys1283Asn Uncertain significance ★ ⚠ same condition
DSCAM p.Lys391Arg Uncertain significance ★ ⚠ same condition
DSCAM p.Met1548Ile Uncertain significance ★ ⚠ same condition
DSCAM p.Thr485Ile Uncertain significance ★ ⚠ same condition
DSCAM c.5036-2A>G 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-thr62 (accessed [today's date]).

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