Is PDE4B p.Leu642= (c.1926C>T) pathogenic?

PDE4B p.Leu642= (c.1926C>T) is classified Benign in PDE4B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.15%, nfe).

How common is PDE4B p.Leu642= (c.1926C>T) in the general population?

PDE4B p.Leu642= (c.1926C>T) is low-frequency (popmax 1.15%, nfe) (gnomAD).

PDE4B p.Leu642=

c.1926C>T · rs79722858 · VCV708064

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP 1.1, phastCons 1
Overall
CADD	5.379	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% European (non-Finnish) · 13,563/1,179,902 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 1.01% 16,321/1,613,972 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.14%	47
Finnishnot grpmax-eligible	1.67%	60
European (non-Finnish)grpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.798%	125
Admixed American	0.34%	294
South Asian	0.24%	416
African / African-American	0.164%	610
Middle Eastern	0.148%	674
East Asian	0.00223%	44,886

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PDE4B
Protein: p.Leu642=
Coding: c.1926C>T
MANE Select: NM_002600
dbSNP: rs79722858
Type: single nucleotide variant
Location: chr1:66372393 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.22 · 43 PDB
Residue 642: the pdease domain; an α-helix

Full PDE4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE4B p.Arg596= Benign ★★ same type
PDE4B p.Ser703Cys Benign ★★ ⚠ same type
PDE4B p.Ala148Val Uncertain significance ★ ⚠ same type
PDE4B p.Arg130Cys Uncertain significance ★ ⚠ same type
PDE4B p.Arg503Cys Uncertain significance ★ ⚠ same type
PDE4B p.Arg552His Uncertain significance ★ ⚠ same type
PDE4B p.Arg576Pro Uncertain significance ★ ⚠ same type
PDE4B p.Arg581Cys Uncertain significance ★ ⚠ 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/pde4b-p-leu642 (accessed [today's date]).

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