Is PDE6A p.Ala39Pro (c.115G>C) pathogenic?

PDE6A p.Ala39Pro (c.115G>C) is classified Uncertain significance in PDE6A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.0866); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PDE6A p.Ala39Pro (c.115G>C)?

PDE6A p.Ala39Pro (c.115G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PDE6A p.Ala39Pro (c.115G>C) in the general population?

PDE6A p.Ala39Pro (c.115G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE6A p.Ala39Pro (c.115G>C)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

PDE6A p.Ala39Pro

c.115G>C · rs2480712763 · VCV2599728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,868)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.65	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 0.99	GERP -2.1, phastCons 0.47
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.94 · regional, not allelic
Overall
CADD	14.93	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 1,613,868). 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: PDE6A
Protein: p.Ala39Pro
Coding: c.115G>C
MANE Select: NM_000440
dbSNP: rs2480712763
Type: single nucleotide variant
Location: chr5:149944559 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE6A p.Ala766Gly Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg236Leu Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg237Cys Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg237His Uncertain significance ★★ same condition
PDE6A p.Arg257Gln Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg267Cys Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg306Gly Uncertain significance ★★ ⚠ same condition
PDE6A p.Arg554Cys Uncertain significance ★★ ⚠ 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/pde6a-p-ala39pro (accessed [today's date]).

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