Is PDE6B p.Pro115Ala (c.343C>G) pathogenic?

PDE6B p.Pro115Ala (c.343C>G) is classified Benign/Likely benign in PDE6B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0721); Rare (popmax 0.758%, afr).

How common is PDE6B p.Pro115Ala (c.343C>G) in the general population?

PDE6B p.Pro115Ala (c.343C>G) is rare (popmax 0.758%, afr) (gnomAD).

What do computational predictors say about PDE6B p.Pro115Ala (c.343C>G)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

PDE6B p.Pro115Ala

c.343C>G · rs147382017 · VCV730671

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.758%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.52	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 0.6	GERP -4.1, phastCons 0.16
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	12.89	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 0.758% African / African-American · 564/74,416 alleles

Filtering AF 0.706% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.686%

Overall 0.0424% 671/1,584,228 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.758%	132
Middle Eastern	0.0666%	1,501
Remaining individualsnot grpmax-eligible	0.0505%	1,980
Admixed American	0.0412%	2,430
European (non-Finnish)	0.00403%	24,793
South Asian	0.00228%	43,834

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.Pro115Ala
Coding: c.343C>G
MANE Select: NM_000283
dbSNP: rs147382017
Type: single nucleotide variant
Location: chr4:625969 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 115: the gaf 1 domain

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

Similar variants

PDE6B p.Pro115Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PDE6B p.Pro115= Likely benign ★ same residue
PDE6B c.1059+2T>G Likely pathogenic ★★ same type
PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1107+1G>T Likely pathogenic ★★ same type
PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1468-2A>G Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1832+1G>T Pathogenic ★★ same type

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-pro115ala (accessed [today's date]).

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