Is WDR19 p.Leu1069= (c.3205C>T) pathogenic?

WDR19 p.Leu1069= (c.3205C>T) is classified Likely benign in WDR19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). Very rare (popmax 8.69e-05%, nfe); Associated with Senior-Loken syndrome 8.

What condition is associated with WDR19 p.Leu1069= (c.3205C>T)?

WDR19 p.Leu1069= (c.3205C>T) is associated with Senior-Loken syndrome 8, asphyxiating thoracic dystrophy 5 (ClinVar).

How common is WDR19 p.Leu1069= (c.3205C>T) in the general population?

WDR19 p.Leu1069= (c.3205C>T) is very rare (popmax 8.69e-05%, nfe) (gnomAD).

How is Senior-Loken syndrome inherited?

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

WDR19 p.Leu1069=

c.3205C>T · VCV4785066

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.69e-05%, nfe)

Conditions

Senior-Loken syndrome 8

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 0.17	GERP 0.8, phastCons 0.004
Overall
CADD	8.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.69e-05% European (non-Finnish) · 1/1,150,478 alleles

Overall 6.42e-05% 1/1,557,866 alleles · very rare exomes 0/1,405,676 · genomes 1/152,190 · joint denominator

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: WDR19
Protein: p.Leu1069=
Coding: c.3205C>T
MANE Select: NM_025132
Type: single nucleotide variant
Location: chr4:39266084 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.44 · 4 PDB
Residue 1069: an α-helix

Full WDR19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Senior-Loken syndrome 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 5

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

WDR19 c.1135-2A>G Likely pathogenic ★★ same condition
WDR19 c.1250-1G>A Pathogenic/Likely pathogenic ★★ same condition
WDR19 c.1778-1G>A Likely pathogenic ★★ same condition
WDR19 c.1982+2T>C Pathogenic/Likely pathogenic ★★ same condition
WDR19 c.2363+1G>A Pathogenic/Likely pathogenic ★★ same condition
WDR19 c.2364-2A>G Likely pathogenic ★★ same condition
WDR19 c.2646-2A>G Likely pathogenic ★★ same condition
WDR19 c.3184-2A>C 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/wdr19-p-leu1069 (accessed [today's date]).

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