Is DSCAM p.Thr1184Ser (c.3551C>G) pathogenic?

DSCAM p.Thr1184Ser (c.3551C>G) is classified Uncertain significance in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: ambiguous (0.509); Very rare (popmax 0.0028%, nfe).

How common is DSCAM p.Thr1184Ser (c.3551C>G) in the general population?

DSCAM p.Thr1184Ser (c.3551C>G) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about DSCAM p.Thr1184Ser (c.3551C>G)?

AlphaMissense predicts ambiguous (score 0.509) — an in-silico prediction, not a clinical call.

DSCAM p.Thr1184Ser

c.3551C>G · rs961228091 · VCV1493302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Computational evidence

Protein change
AlphaMissense	0.509	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -12.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.61, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 147 kb · p 2e-13 · regional, not allelic
Overall
CADD	25.4	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 0.0028% European (non-Finnish) · 33/1,177,008 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00224% 36/1,607,250 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,667
African / African-American	0.00268%	37,265
Remaining individualsnot grpmax-eligible	0.00161%	62,162

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.Thr1184Ser
Coding: c.3551C>G
MANE Select: NM_001389
dbSNP: rs961228091
Type: single nucleotide variant
Location: chr21:40133865 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 1184: the fibronectin type-iii 3 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-thr1184ser (accessed [today's date]).

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