Is CDC16 p.Ile475Phe (c.1423A>T) pathogenic?

CDC16 p.Ile475Phe (c.1423A>T) is classified Uncertain significance in CDC16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.336); Very rare (popmax 0.00446%, eas).

How common is CDC16 p.Ile475Phe (c.1423A>T) in the general population?

CDC16 p.Ile475Phe (c.1423A>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CDC16 p.Ile475Phe (c.1423A>T)?

AlphaMissense predicts likely benign (score 0.336) — an in-silico prediction, not a clinical call.

CDC16 p.Ile475Phe

c.1423A>T · rs202210151 · VCV3140778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.336	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 0.00031 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00131% 2/152,322 alleles · very rare

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: CDC16
Protein: p.Ile475Phe
Coding: c.1423A>T
MANE Select: NM_001078645
dbSNP: rs202210151
Type: single nucleotide variant
Location: chr13:114262925 (GRCh38)
Gene constraint: LOEUF 0.657 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 21 PDB
Residue 475: a β-strand

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.Ala536Ser Uncertain significance ★ ⚠ same type
CDC16 p.Ala57Thr 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-ile475phe (accessed [today's date]).

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