Is PDE6C p.Phe530Ser (c.1589T>C) pathogenic?

PDE6C p.Phe530Ser (c.1589T>C) is classified Likely pathogenic in PDE6C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-13). AlphaMissense: ambiguous (0.3721); Absent from gnomAD v4.1; Associated with cone dystrophy 4.

What condition is associated with PDE6C p.Phe530Ser (c.1589T>C)?

PDE6C p.Phe530Ser (c.1589T>C) is associated with cone dystrophy 4 (ClinVar).

How common is PDE6C p.Phe530Ser (c.1589T>C) in the general population?

PDE6C p.Phe530Ser (c.1589T>C) is absent from gnomAD v4.1 (gnomAD).

How is Progressive cone dystrophy inherited?

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

What do computational predictors say about PDE6C p.Phe530Ser (c.1589T>C)?

AlphaMissense predicts ambiguous (score 0.3721) — an in-silico prediction, not a clinical call.

PDE6C p.Phe530Ser

c.1589T>C · rs1564801134 · VCV599170

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3721 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cone dystrophy 4

Computational evidence

Protein change
AlphaMissense	0.3721	ambiguous
REVEL	0.614	indeterminate
SaProt	LLR -13.19	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.86, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

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: PDE6C
Protein: p.Phe530Ser
Coding: c.1589T>C
MANE Select: NM_006204
dbSNP: rs1564801134
Type: single nucleotide variant
Location: chr10:93640176 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.53 · 7 PDB
Residue 530: a UniProt-annotated variant site (in achm5); the pdease domain; an α-helix

Full PDE6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone dystrophy 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive cone dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult

Similar variants

PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg259Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg29Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PDE6C p.Arg527Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg557Ter Pathogenic/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/pde6c-p-phe530ser (accessed [today's date]).

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