Is PDE6A p.Leu36Phe (c.106C>T) pathogenic?

PDE6A p.Leu36Phe (c.106C>T) is classified Uncertain significance in PDE6A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). AlphaMissense: likely benign (0.1023); Absent from gnomAD v4.1.

How common is PDE6A p.Leu36Phe (c.106C>T) in the general population?

PDE6A p.Leu36Phe (c.106C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE6A p.Leu36Phe (c.106C>T)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

PDE6A p.Leu36Phe

c.106C>T · rs1393711147 · VCV1395687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.25	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 3.9	GERP -1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.94 · regional, not allelic
Overall
CADD	18.49	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

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: PDE6A
Protein: p.Leu36Phe
Coding: c.106C>T
MANE Select: NM_000440
dbSNP: rs1393711147
Type: single nucleotide variant
Location: chr5:149944568 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80

Full PDE6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1263+1G>T Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1620+1G>A Pathogenic ★★ same type
PDE6A c.1620+2T>A Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1926+1G>A Pathogenic ★★ same type
PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same type
PDE6A c.2027+2T>G Pathogenic/Likely pathogenic ★★ same type

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/pde6a-p-leu36phe (accessed [today's date]).

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