Is PDE6A p.Val115Ile (c.343G>A) pathogenic?

PDE6A p.Val115Ile (c.343G>A) is classified Conflicting classifications of pathogenicity in PDE6A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0797); Rare (popmax 0.236%, afr); Associated with Inborn genetic diseases.

What condition is associated with PDE6A p.Val115Ile (c.343G>A)?

PDE6A p.Val115Ile (c.343G>A) is associated with Inborn genetic diseases, retinitis pigmentosa (ClinVar).

How common is PDE6A p.Val115Ile (c.343G>A) in the general population?

PDE6A p.Val115Ile (c.343G>A) is rare (popmax 0.236%, afr) (gnomAD).

What do computational predictors say about PDE6A p.Val115Ile (c.343G>A)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

PDE6A p.Val115Ile

c.343G>A · rs147159579 · VCV352003

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.236%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -7.75	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 6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.94 · regional, not allelic
Overall
CADD	20.8	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 0.236% African / African-American · 177/75,010 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.0136% 219/1,614,078 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.236%	424
South Asian	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.0117%	8,572
European (non-Finnish)	0.000169%	589,998

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.Val115Ile
Coding: c.343G>A
MANE Select: NM_000440
dbSNP: rs147159579
Type: single nucleotide variant
Location: chr5:149944331 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 115: the gaf 1 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: retinitis pigmentosa

Similar variants

PDE6A p.Val115= Likely benign ★ 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-val115ile (accessed [today's date]).

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