Is GUCY2D p.Pro47Arg (c.140C>G) pathogenic?

GUCY2D p.Pro47Arg (c.140C>G) is classified Uncertain significance in GUCY2D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.0847); No allele count reported in gnomAD v4.1 (AN 1,517,160); Associated with cone-rod dystrophy 6.

What condition is associated with GUCY2D p.Pro47Arg (c.140C>G)?

GUCY2D p.Pro47Arg (c.140C>G) is associated with cone-rod dystrophy 6, Leber congenital amaurosis 1 (ClinVar).

How common is GUCY2D p.Pro47Arg (c.140C>G) in the general population?

GUCY2D p.Pro47Arg (c.140C>G) is no allele count reported in gnomAD v4.1 (AN 1,517,160) (gnomAD).

How is Cone rod dystrophy inherited?

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

What do computational predictors say about GUCY2D p.Pro47Arg (c.140C>G)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

GUCY2D p.Pro47Arg

c.140C>G · rs1014118881 · VCV1719460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,517,160)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cone-rod dystrophy 6

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.3, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 12 kb · p 0.34 · regional, not allelic
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,517,160). 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: GUCY2D
Protein: p.Pro47Arg
Coding: c.140C>G
MANE Select: NM_000180
dbSNP: rs1014118881
Type: single nucleotide variant
Location: chr17:8003187 (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.Pro47Ser Uncertain significance ★ ⚠ same residue
GUCY2D p.Pro47= Likely benign ★ 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-pro47arg (accessed [today's date]).

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