Is WDR72 p.Pro559Arg (c.1676C>G) pathogenic?

WDR72 p.Pro559Arg (c.1676C>G) is classified Uncertain significance in WDR72 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: ambiguous (0.3519); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with WDR72 p.Pro559Arg (c.1676C>G)?

WDR72 p.Pro559Arg (c.1676C>G) is associated with Inborn genetic diseases (ClinVar).

How common is WDR72 p.Pro559Arg (c.1676C>G) in the general population?

WDR72 p.Pro559Arg (c.1676C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about WDR72 p.Pro559Arg (c.1676C>G)?

AlphaMissense predicts ambiguous (score 0.3519) — an in-silico prediction, not a clinical call.

WDR72 p.Pro559Arg

c.1676C>G · rs151224179 · VCV2470176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3519	ambiguous
REVEL	0.724	pathogenic-leaning
SaProt	LLR -9.87	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 215 kb · p 0.0025 · regional, not allelic
Overall
CADD	26.6	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 0.00534% African / African-American · 4/74,900 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,996 alleles · very rare exomes 1/1,461,888 · genomes 3/152,108 · 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: WDR72
Protein: p.Pro559Arg
Coding: c.1676C>G
MANE Select: NM_182758
dbSNP: rs151224179
Type: single nucleotide variant
Location: chr15:53699839 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.22

Full WDR72 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

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WDR72 p.Ala795Thr Uncertain significance ★★ same condition
WDR72 p.Arg322Ser Uncertain significance ★★ ⚠ same condition
WDR72 p.Arg525Lys Uncertain significance ★★ ⚠ same condition
WDR72 p.Asp1071His Uncertain significance ★★ ⚠ same condition
WDR72 p.Asp393Asn Uncertain significance ★★ ⚠ same condition
WDR72 p.Asp495Val 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/wdr72-p-pro559arg (accessed [today's date]).

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