Is CDC14B p.Ile249Val (c.745A>G) pathogenic?

CDC14B p.Ile249Val (c.745A>G) is classified Uncertain significance in CDC14B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.00268%, afr).

How common is CDC14B p.Ile249Val (c.745A>G) in the general population?

CDC14B p.Ile249Val (c.745A>G) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about CDC14B p.Ile249Val (c.745A>G)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

CDC14B p.Ile249Val

c.745A>G · VCV4650793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 0.81, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 116 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	18.7	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 0.00268% African / African-American · 2/74,750 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000187% 3/1,608,208 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,375
Remaining individualsnot grpmax-eligible	0.00161%	62,256

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.Ile249Val
Coding: c.745A>G
MANE Select: NM_033331
Type: single nucleotide variant
Location: chr9:96534128 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 81.04 · 3 PDB
Residue 249: the tyrosine-protein phosphatase domain; an α-helix; the 'b' 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-ile249val (accessed [today's date]).

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