Is SYNCRIP p.Gln492fs (c.1473dup) pathogenic?

SYNCRIP p.Gln492fs (c.1473dup) is classified Pathogenic in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Associated with SYNCRIP-related neurodevelopmental disorder.

What condition is associated with SYNCRIP p.Gln492fs (c.1473dup)?

SYNCRIP p.Gln492fs (c.1473dup) is associated with SYNCRIP-related neurodevelopmental disorder (ClinVar).

SYNCRIP p.Gln492fs

c.1473dup · VCV4532038

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SYNCRIP-related neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: SYNCRIP
Protein: p.Gln492fs
Coding: c.1473dup
MANE Select: NM_006372
Type: Duplication
Location: chr6:85615154 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 492: the 'interaction with apobec1' region; the '8 x 3 aa repeats of r-g-g' region

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

Disease context

SYNCRIP-related neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SYNCRIP p.Ala374Glu Uncertain significance ★ ⚠ same condition
SYNCRIP p.Gly505Val Uncertain significance ★ ⚠ same condition
SYNCRIP p.Pro437Ser Uncertain significance ★ ⚠ same condition
SYNCRIP p.Tyr456Ter Uncertain significance ★ same condition
SYNCRIP p.Pro147fs Likely pathogenic ★ same type
SYNCRIP p.Asn285fs Uncertain significance ★ 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/syncrip-p-gln492fs (accessed [today's date]).

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