Is DSCAM p.Arg388Leu (c.1163G>T) pathogenic?

DSCAM p.Arg388Leu (c.1163G>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-22). AlphaMissense: ambiguous (0.4967); Very rare (popmax 0.00891%, eas); Associated with DSCAM-related disorder.

What condition is associated with DSCAM p.Arg388Leu (c.1163G>T)?

DSCAM p.Arg388Leu (c.1163G>T) is associated with DSCAM-related disorder (ClinVar).

How common is DSCAM p.Arg388Leu (c.1163G>T) in the general population?

DSCAM p.Arg388Leu (c.1163G>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DSCAM p.Arg388Leu (c.1163G>T)?

AlphaMissense predicts ambiguous (score 0.4967) — an in-silico prediction, not a clinical call.

DSCAM p.Arg388Leu

c.1163G>T · rs369481071 · VCV2634419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DSCAM-related disorder

Computational evidence

Protein change
AlphaMissense	0.4967	ambiguous
REVEL	0.644	pathogenic-leaning
SaProt	LLR -10.17	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	25.2	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 0.00891% East Asian · 4/44,890 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000682% 11/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
South Asian	0.00439%	22,773
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00133%	74,934

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.Arg388Leu
Coding: c.1163G>T
MANE Select: NM_001389
dbSNP: rs369481071
Type: single nucleotide variant
Location: chr21:40347717 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 388: the ig-like c2-type 4 domain

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

Disease context

DSCAM-related disorder

Similar variants

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
DSCAM p.Arg1657Ter Uncertain significance same condition
DSCAM p.Arg241His 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-arg388leu (accessed [today's date]).

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