Is PDE6A p.Met1Val (c.1A>G) pathogenic?

PDE6A p.Met1Val (c.1A>G) is classified Likely pathogenic in PDE6A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-07). Very rare (popmax 0.00017%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PDE6A p.Met1Val (c.1A>G)?

PDE6A p.Met1Val (c.1A>G) is associated with retinitis pigmentosa (ClinVar).

How common is PDE6A p.Met1Val (c.1A>G) in the general population?

PDE6A p.Met1Val (c.1A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6A p.Met1Val

c.1A>G · rs976670244 · VCV636055

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.454	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Overall
CADD	22.6	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 0.00017% European (non-Finnish) · 2/1,175,030 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,450,640 alleles · very rare

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: PDE6A
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_000440
dbSNP: rs976670244
Type: single nucleotide variant
Location: chr5:149944673 (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

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PDE6A p.Met1Thr Likely pathogenic ★★ same residue
PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.1620+1G>A Pathogenic ★★ same condition
PDE6A c.1926+1G>A Pathogenic ★★ same condition
PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.627+2T>G Pathogenic ★★ same condition
PDE6A c.998+1G>A Pathogenic ★★ same condition
PDE6A p.Arg102Cys 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/pde6a-p-met1val (accessed [today's date]).

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