Is DSCAM p.Val591Leu (c.1771G>T) pathogenic?

DSCAM p.Val591Leu (c.1771G>T) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: ambiguous (0.4087); Very rare (popmax 0.0072%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSCAM p.Val591Leu (c.1771G>T)?

DSCAM p.Val591Leu (c.1771G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSCAM p.Val591Leu (c.1771G>T) in the general population?

DSCAM p.Val591Leu (c.1771G>T) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about DSCAM p.Val591Leu (c.1771G>T)?

AlphaMissense predicts ambiguous (score 0.4087) — an in-silico prediction, not a clinical call.

DSCAM p.Val591Leu

c.1771G>T · rs376716215 · VCV2272117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4087	ambiguous
REVEL	0.241	benign-leaning
SaProt	LLR -6.56	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	24.0	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 0.0072% European (non-Finnish) · 85/1,180,010 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00551% 89/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,882
Remaining individualsnot grpmax-eligible	0.0048%	20,819
African / African-American	0.00133%	74,948

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.Val591Leu
Coding: c.1771G>T
MANE Select: NM_001389
dbSNP: rs376716215
Type: single nucleotide variant
Location: chr21:40338113 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 591: 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.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-val591leu (accessed [today's date]).

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