Is PDE6B p.Pro158Ser (c.472C>T) pathogenic?

PDE6B p.Pro158Ser (c.472C>T) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-06). AlphaMissense: likely benign (0.0743); Ultra-rare (popmax 0.0681%, sas); Associated with Inborn genetic diseases.

What condition is associated with PDE6B p.Pro158Ser (c.472C>T)?

PDE6B p.Pro158Ser (c.472C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDE6B p.Pro158Ser (c.472C>T) in the general population?

PDE6B p.Pro158Ser (c.472C>T) is ultra-rare (popmax 0.0681%, sas) (gnomAD).

What do computational predictors say about PDE6B p.Pro158Ser (c.472C>T)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

PDE6B p.Pro158Ser

c.472C>T · rs779281806 · VCV1657858

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -8.59	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 0.13	GERP -2.3
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	7.016	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 0.0681% South Asian · 62/91,070 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.00422% 68/1,612,422 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0681%	1,469
Remaining individualsnot grpmax-eligible	0.00801%	12,483
Admixed American	0.00167%	59,996

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.Pro158Ser
Coding: c.472C>T
MANE Select: NM_000283
dbSNP: rs779281806
Type: single nucleotide variant
Location: chr4:634680 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 158: the gaf 1 domain

Full PDE6B 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

Similar variants

PDE6B p.Ala19Ser Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala341Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala34Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala589Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala809Val Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala845Glu Uncertain significance ★★ ⚠ same condition
PDE6B p.Arg304Cys Uncertain significance ★★ ⚠ same condition
PDE6B p.Arg531Pro Uncertain significance ★★ ⚠ 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/pde6b-p-pro158ser (accessed [today's date]).

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