Is PDE6A p.Val784Ile (c.2350G>A) pathogenic?

PDE6A p.Val784Ile (c.2350G>A) is classified Uncertain significance in PDE6A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-20). AlphaMissense: ambiguous (0.4911); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with PDE6A p.Val784Ile (c.2350G>A)?

PDE6A p.Val784Ile (c.2350G>A) is associated with Inborn genetic diseases, inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

How common is PDE6A p.Val784Ile (c.2350G>A) in the general population?

PDE6A p.Val784Ile (c.2350G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PDE6A p.Val784Ile (c.2350G>A)?

AlphaMissense predicts ambiguous (score 0.4911) — an in-silico prediction, not a clinical call.

PDE6A p.Val784Ile

c.2350G>A · rs746482403 · VCV905268

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4911	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -9.01	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 6,871 bp · p 0.14 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00143% 23/1,612,090 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
South Asian	0.0033%	30,346
East Asian	0.00223%	44,894
European (non-Finnish)	0.00144%	69,312

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.Val784Ile
Coding: c.2350G>A
MANE Select: NM_000440
dbSNP: rs746482403
Type: single nucleotide variant
Location: chr5:149866178 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 784: the pdease domain

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

Also linked: inherited retinal dystrophy retinitis pigmentosa

Similar variants

PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.1407+1G>C 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-val784ile (accessed [today's date]).

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