Is GUCY2D p.Pro47= (c.141C>G) pathogenic?

GUCY2D p.Pro47= (c.141C>G) is classified Likely benign in GUCY2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). Absent from gnomAD v4.1; Associated with cone-rod dystrophy 6.

What condition is associated with GUCY2D p.Pro47= (c.141C>G)?

GUCY2D p.Pro47= (c.141C>G) is associated with cone-rod dystrophy 6, Leber congenital amaurosis 1 (ClinVar).

How common is GUCY2D p.Pro47= (c.141C>G) in the general population?

GUCY2D p.Pro47= (c.141C>G) is absent from gnomAD v4.1 (gnomAD).

How is Cone rod dystrophy inherited?

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

GUCY2D p.Pro47=

c.141C>G · rs1482857964 · VCV1621240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cone-rod dystrophy 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -0.004, phastCons 0.002
Overall
CADD	4.838	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: GUCY2D
Protein: p.Pro47=
Coding: c.141C>G
MANE Select: NM_000180
dbSNP: rs1482857964
Type: single nucleotide variant
Location: chr17:8003188 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.37

Full GUCY2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis 1

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

GUCY2D p.Pro47Leu Uncertain significance ★★ ⚠ same residue
GUCY2D p.Pro47Arg Uncertain significance ★ ⚠ same residue
GUCY2D p.Pro47Ser Uncertain significance ★ ⚠ same residue
GUCY2D c.1956+1G>A Pathogenic ★★★ same condition
GUCY2D c.3224+1G>C Pathogenic ★★★ same condition
GUCY2D c.3224+3G>T Likely pathogenic ★★★ same condition
GUCY2D p.Ala946Thr Likely pathogenic ★★★ same condition
GUCY2D p.Arg1091Ter Pathogenic ★★★ 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/gucy2d-p-pro47 (accessed [today's date]).

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