Is WDR19 p.Phe5Ser (c.14T>C) pathogenic?

WDR19 p.Phe5Ser (c.14T>C) is classified Pathogenic/Likely pathogenic in WDR19 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-02). AlphaMissense: likely pathogenic (0.7443); Very rare (popmax 0.000784%, nfe); Associated with asphyxiating thoracic dystrophy 5.

What condition is associated with WDR19 p.Phe5Ser (c.14T>C)?

WDR19 p.Phe5Ser (c.14T>C) is associated with asphyxiating thoracic dystrophy 5, nephronophthisis 13, cranioectodermal dysplasia 4 (ClinVar).

How common is WDR19 p.Phe5Ser (c.14T>C) in the general population?

WDR19 p.Phe5Ser (c.14T>C) is very rare (popmax 0.000784%, nfe) (gnomAD).

What do computational predictors say about WDR19 p.Phe5Ser (c.14T>C)?

AlphaMissense predicts likely pathogenic (score 0.7443) — an in-silico prediction, not a clinical call.

WDR19 p.Phe5Ser

c.14T>C · rs1237494778 · VCV562401

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000784%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

asphyxiating thoracic dystrophy 5

Computational evidence

Protein change
AlphaMissense	0.7443	likely pathogenic ✓ concordant with ClinVar
REVEL	0.633	indeterminate
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 96 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	26.1	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 0.000784% European (non-Finnish) · 9/1,148,610 alleles

Filtering AF 0.000369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000267%

Overall 0.000579% 9/1,554,976 alleles · very rare exomes 8/1,402,786 · 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.Phe5Ser
Coding: c.14T>C
MANE Select: NM_025132
dbSNP: rs1237494778
Type: single nucleotide variant
Location: chr4:39185733 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.44 · 4 PDB
Residue 5: a β-strand

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: nephronophthisis 13 cranioectodermal dysplasia 4 Senior-Loken syndrome 8 spermatogenic failure 72

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-phe5ser (accessed [today's date]).

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