Is DSCAM p.Lys511Glu (c.1531A>G) pathogenic?

DSCAM p.Lys511Glu (c.1531A>G) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.3381); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Lys511Glu (c.1531A>G)?

DSCAM p.Lys511Glu (c.1531A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Lys511Glu (c.1531A>G) in the general population?

DSCAM p.Lys511Glu (c.1531A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DSCAM p.Lys511Glu (c.1531A>G)?

AlphaMissense predicts likely benign (score 0.3381) — an in-silico prediction, not a clinical call.

DSCAM p.Lys511Glu

c.1531A>G · VCV3842541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3381 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3381	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 508 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	25.4	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 6.84e-05%

Overall 6.84e-05% 1/1,461,470 alleles · very rare

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.Lys511Glu
Coding: c.1531A>G
MANE Select: NM_001389
Type: single nucleotide variant
Location: chr21:40338353 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 511: the ig-like c2-type 6 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.Lys511Arg 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-lys511glu (accessed [today's date]).

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