Is WDR19 p.Pro219= (c.657A>G) pathogenic?

WDR19 p.Pro219= (c.657A>G) is classified Likely benign in WDR19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). Very rare (popmax 0.00171%, amr); Associated with asphyxiating thoracic dystrophy 5.

What condition is associated with WDR19 p.Pro219= (c.657A>G)?

WDR19 p.Pro219= (c.657A>G) is associated with asphyxiating thoracic dystrophy 5, Senior-Loken syndrome 8 (ClinVar).

How common is WDR19 p.Pro219= (c.657A>G) in the general population?

WDR19 p.Pro219= (c.657A>G) is very rare (popmax 0.00171%, amr) (gnomAD).

WDR19 p.Pro219=

c.657A>G · VCV3752292

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

asphyxiating thoracic dystrophy 5

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 0.56	GERP -0.59, phastCons 0.86
Overall
CADD	7.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,514 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00025% 4/1,603,150 alleles · very rare exomes 4/1,450,824 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,514
European (non-Finnish)	0.000255%	391,471

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.Pro219=
Coding: c.657A>G
MANE Select: NM_025132
Type: single nucleotide variant
Location: chr4:39205207 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.44 · 4 PDB

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

Disease context

asphyxiating thoracic dystrophy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Senior-Loken syndrome 8

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-pro219 (accessed [today's date]).

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