Is CDC14B p.Ser483Arg (c.1449C>G) pathogenic?

CDC14B p.Ser483Arg (c.1449C>G) is classified Uncertain significance in CDC14B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: ambiguous (0.4713); Ultra-rare (popmax 0.0159%, nfe).

How common is CDC14B p.Ser483Arg (c.1449C>G) in the general population?

CDC14B p.Ser483Arg (c.1449C>G) is ultra-rare (popmax 0.0159%, nfe) (gnomAD).

What do computational predictors say about CDC14B p.Ser483Arg (c.1449C>G)?

AlphaMissense predicts ambiguous (score 0.4713) — an in-silico prediction, not a clinical call.

CDC14B p.Ser483Arg

c.1449C>G · rs143630684 · VCV2570378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4713	ambiguous
REVEL	0.46	indeterminate
SaProt	LLR -8.05	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 116 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	24.5	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 0.0159% European (non-Finnish) · 185/1,164,950 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.0118% 189/1,597,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0159%	6,297
Admixed American	0.00334%	29,947
Remaining individualsnot grpmax-eligible	0.00323%	30,959

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: CDC14B
Protein: p.Ser483Arg
Coding: c.1449C>G
MANE Select: NM_033331
dbSNP: rs143630684
Type: single nucleotide variant
Location: chr9:96509684 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 81.04 · 3 PDB
Residue 483: the 'disordered' region

Full CDC14B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC14B p.Ala13Thr Uncertain significance ★ ⚠ same type
CDC14B p.Ala13Val Uncertain significance ★ ⚠ same type
CDC14B p.Ala14Ser Uncertain significance ★ ⚠ same type
CDC14B p.Ala286Val Uncertain significance ★ ⚠ same type
CDC14B p.Ala388Val Uncertain significance ★ ⚠ same type
CDC14B p.Ala87Thr Uncertain significance ★ ⚠ same type
CDC14B p.Ala95Val Uncertain significance ★ ⚠ same type
CDC14B p.Arg266Lys 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/cdc14b-p-ser483arg (accessed [today's date]).

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