Is CLN3 p.Gln352= (c.1056G>A) pathogenic?

CLN3 p.Gln352= (c.1056G>A) is classified Uncertain significance in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with CLN3 p.Gln352= (c.1056G>A)?

CLN3 p.Gln352= (c.1056G>A) is associated with retinitis pigmentosa (ClinVar).

How common is CLN3 p.Gln352= (c.1056G>A) in the general population?

CLN3 p.Gln352= (c.1056G>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CLN3 p.Gln352=

c.1056G>A · VCV3544492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.89	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.66	loss · gain 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 0.45, phastCons 1
Overall
CADD	20.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLN3
Protein: p.Gln352=
Coding: c.1056G>A
MANE Select: NM_001042432
Type: single nucleotide variant
Location: chr16:28482105 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81

Full CLN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CLN3 p.Gln352Ter Pathogenic ★★ same residue
CLN3 p.Gln352His Likely pathogenic same residue
CLN3 p.Arg405Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN3 p.Ser171Phe Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Val330Ile Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN3 p.Gln204Pro Uncertain significance ★★ ⚠ same condition
CLN3 p.Ile285Val Uncertain significance ★★ ⚠ same condition
CLN3 p.Ser423Leu 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/cln3-p-gln352 (accessed [today's date]).

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