Is PDE6B p.Val316Met (c.946G>A) pathogenic?

PDE6B p.Val316Met (c.946G>A) is classified Uncertain significance in PDE6B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-29). AlphaMissense: likely benign (0.2797); Ultra-rare (popmax 0.0167%, mid); Associated with retinitis pigmentosa 40.

What condition is associated with PDE6B p.Val316Met (c.946G>A)?

PDE6B p.Val316Met (c.946G>A) is associated with retinitis pigmentosa 40 (ClinVar).

How common is PDE6B p.Val316Met (c.946G>A) in the general population?

PDE6B p.Val316Met (c.946G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about PDE6B p.Val316Met (c.946G>A)?

AlphaMissense predicts likely benign (score 0.2797) — an in-silico prediction, not a clinical call.

PDE6B p.Val316Met

c.946G>A · rs200694314 · VCV1803155

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa 40

Computational evidence

Protein change
AlphaMissense	0.2797	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7	GERP -2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.0167% Middle Eastern · 1/5,986 alleles

Filtering AF 0.00725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00673%

Overall 0.00686% 108/1,573,238 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,986
European (non-Finnish)	0.00866%	11,545
Admixed American	0.00502%	19,935
African / African-American	0.00269%	37,114
South Asian	0.00222%	45,129
Remaining individualsnot grpmax-eligible	0.00163%	61,186

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: PDE6B
Protein: p.Val316Met
Coding: c.946G>A
dbSNP: rs200694314
Type: single nucleotide variant
Location: chr4:654842 (GRCh38)

Full PDE6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 40 — 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)

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/pde6b-p-val316met (accessed [today's date]).

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