Is PDE6C p.Leu84Pro (c.251T>C) pathogenic?

PDE6C p.Leu84Pro (c.251T>C) is classified Likely pathogenic in PDE6C (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-29). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with PDE6C-related disorder.

What condition is associated with PDE6C p.Leu84Pro (c.251T>C)?

PDE6C p.Leu84Pro (c.251T>C) is associated with PDE6C-related disorder (ClinVar).

How common is PDE6C p.Leu84Pro (c.251T>C) in the general population?

PDE6C p.Leu84Pro (c.251T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE6C p.Leu84Pro (c.251T>C)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

PDE6C p.Leu84Pro

c.251T>C · rs2058399145 · VCV866137

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PDE6C-related disorder

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic ✓ concordant with ClinVar · top 8% in PDE6C
REVEL	0.907	moderately pathogenic-leaning
SaProt	LLR -16.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	27.6	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.Leu84Pro
Coding: c.251T>C
MANE Select: NM_006204
dbSNP: rs2058399145
Type: single nucleotide variant
Location: chr10:93612976 (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 84: the gaf 1 domain; an α-helix

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

Disease context

PDE6C-related disorder

Similar variants

PDE6C p.Leu84= Conflicting classifications of pathogenicity ★ same residue
PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.481-1G>A Likely pathogenic ★★ same condition
PDE6C c.939+2T>G Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg104Trp Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg238Ter 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-leu84pro (accessed [today's date]).

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