Is WDR36 p.Pro754Ser (c.2260C>T) pathogenic?

WDR36 p.Pro754Ser (c.2260C>T) is classified Uncertain significance in WDR36 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00031%).

How common is WDR36 p.Pro754Ser (c.2260C>T) in the general population?

WDR36 p.Pro754Ser (c.2260C>T) is very rare (popmax 0.00031%) (gnomAD).

What do computational predictors say about WDR36 p.Pro754Ser (c.2260C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

WDR36 p.Pro754Ser

c.2260C>T · VCV3469375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00031%)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP 2.9, phastCons 0.028
Regional constraint	o/e 1.15	unconstrained · MANE · 34 kb · p 1.9e-06 · regional, not allelic
Overall
CADD	6.793	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P810S vs ClinVar P754S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00031%

Overall 0.00031% 5/1,613,468 alleles · very rare exomes 4/1,461,348 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,398
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: WDR36
Protein: p.Pro754Ser
Coding: c.2260C>T
MANE Select: NM_139281
Type: single nucleotide variant
Location: chr5:111123916 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.47 · 3 PDB

Full WDR36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WDR36 p.Ala297Ser Uncertain significance ★★ same type
WDR36 p.Ala75Thr Uncertain significance ★★ same type
WDR36 p.Arg374His Uncertain significance ★★ same type
WDR36 p.Arg473Gln Uncertain significance ★★ ⚠ same type
WDR36 p.Asn87Ser Uncertain significance ★★ ⚠ same type
WDR36 p.Asp571His Uncertain significance ★★ ⚠ same type
WDR36 p.Asp686Val Uncertain significance ★★ ⚠ same type
WDR36 p.Glu674Gly 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/wdr36-p-pro754ser (accessed [today's date]).

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