Is SYNCRIP p.Gly522fs (c.1564_1568del) pathogenic?

SYNCRIP p.Gly522fs (c.15641568del) is classified Uncertain significance in SYNCRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-10). No gnomAD frequency available for this variant.

How common is SYNCRIP p.Gly522fs (c.1564_1568del) in the general population?

SYNCRIP p.Gly522fs (c.1564_1568del) is no gnomAD frequency available for this variant (gnomAD).

SYNCRIP p.Gly522fs

c.1564_1568del · rs2537720915 · VCV3253095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5.4	GERP 2.2, 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: SYNCRIP
Protein: p.Gly522fs
Coding: c.1564_1568del
MANE Select: NM_006372
dbSNP: rs2537720915
Type: Deletion
Location: chr6:85615060 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 522: the 'interaction with apobec1' region; the '8 x 3 aa repeats of r-g-g' region; the 'disordered' region; the 'interaction with smn' region

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

Similar variants

SYNCRIP p.Gly522Cys Uncertain significance ★ ⚠ same residue
SYNCRIP p.Gly522Ser Uncertain significance ★ ⚠ same residue
SYNCRIP p.Ala299fs Uncertain significance ★ same type
SYNCRIP p.Asp82_Ser83insTer Uncertain significance ★ same type
SYNCRIP p.Lys284del Uncertain significance ★ same type
SYNCRIP p.Phe405fs Uncertain significance ★ same type
SYNCRIP p.Tyr460fs Uncertain significance ★ same type
SYNCRIP p.Val273_Tyr276del 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-gly522fs (accessed [today's date]).

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