Is GUCY2D p.Ser1007Ter (c.3020C>A) pathogenic?

GUCY2D p.Ser1007Ter (c.3020C>A) is classified Likely pathogenic in GUCY2D (ClinVar, Expert panel, 2 submitters; last evaluated 2025-12-19). Very rare (popmax 0.00167%, amr); Associated with GUCY2D-related recessive retinopathy.

What condition is associated with GUCY2D p.Ser1007Ter (c.3020C>A)?

GUCY2D p.Ser1007Ter (c.3020C>A) is associated with GUCY2D-related recessive retinopathy (ClinVar).

How common is GUCY2D p.Ser1007Ter (c.3020C>A) in the general population?

GUCY2D p.Ser1007Ter (c.3020C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

GUCY2D p.Ser1007Ter

c.3020C>A · VCV4538536

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

GUCY2D-related recessive retinopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,864 alleles

Overall 6.2e-05% 1/1,612,284 alleles · very rare exomes 0/1,460,122 · genomes 1/152,162 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GUCY2D
Protein: p.Ser1007Ter
Coding: c.3020C>A
MANE Select: NM_000180
Type: single nucleotide variant
Location: chr17:8015818 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.37
Residue 1007: a UniProt-annotated variant site (in lca1); the guanylate cyclase domain

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

Disease context

GUCY2D-related recessive retinopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GUCY2D p.Ser1007Leu Conflicting classifications of pathogenicity ★ ⚠ 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 c.722-1G>T Pathogenic ★★★ same condition
GUCY2D p.Ala946Thr Likely pathogenic ★★★ same condition
GUCY2D p.Arg1091Ter Pathogenic ★★★ same condition
GUCY2D p.Arg313Cys Likely 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-ser1007ter (accessed [today's date]).

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