Is SYNGAP1 p.Pro751fs (c.2250dup) pathogenic?

SYNGAP1 p.Pro751fs (c.2250dup) is classified Likely pathogenic in SYNGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-03). No gnomAD frequency available for this variant; Associated with intellectual disability.

What condition is associated with SYNGAP1 p.Pro751fs (c.2250dup)?

SYNGAP1 p.Pro751fs (c.2250dup) is associated with intellectual disability, intellectual disability, autosomal dominant 5 (ClinVar).

How common is SYNGAP1 p.Pro751fs (c.2250dup) in the general population?

SYNGAP1 p.Pro751fs (c.2250dup) is no gnomAD frequency available for this variant (gnomAD).

SYNGAP1 p.Pro751fs

c.2250dup · rs1761049027 · VCV976428

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.2	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SYNGAP1
Protein: p.Pro751fs
Coding: c.2250dup
MANE Select: NM_006772
dbSNP: rs1761049027
Type: Duplication
Location: chr6:33441710 (GRCh38)

Full SYNGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal dominant 5

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/syngap1-p-pro751fs (accessed [today's date]).

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