Is CDC16 p.Ala536Ser (c.1606G>T) pathogenic?

CDC16 p.Ala536Ser (c.1606G>T) is classified Uncertain significance in CDC16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-02). AlphaMissense: likely benign (0.092); Absent from gnomAD v4.1.

How common is CDC16 p.Ala536Ser (c.1606G>T) in the general population?

CDC16 p.Ala536Ser (c.1606G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC16 p.Ala536Ser (c.1606G>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

CDC16 p.Ala536Ser

c.1606G>T · VCV3264931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -5.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 0.00031 · regional, not allelic
Overall
CADD	21.6	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC16
Protein: p.Ala536Ser
Coding: c.1606G>T
MANE Select: NM_001078645
Type: single nucleotide variant
Location: chr13:114272186 (GRCh38)
Gene constraint: LOEUF 0.657 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 21 PDB

Full CDC16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC16 p.Ile132= Benign ★★ same type
CDC16 p.Ala142Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala319Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala44Gly Uncertain significance ★ ⚠ same type
CDC16 p.Ala479Ser Uncertain significance ★ ⚠ same type
CDC16 p.Ala51Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala57Thr Uncertain significance ★ ⚠ same type
CDC16 p.Arg202His 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/cdc16-p-ala536ser (accessed [today's date]).

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