Is CDC14B p.Asn256Ser (c.767A>G) pathogenic?

CDC14B p.Asn256Ser (c.767A>G) is classified Likely benign in CDC14B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely benign (0.0708); Very rare (popmax 0.00102%, nfe).

How common is CDC14B p.Asn256Ser (c.767A>G) in the general population?

CDC14B p.Asn256Ser (c.767A>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CDC14B p.Asn256Ser (c.767A>G)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

CDC14B p.Asn256Ser

c.767A>G · VCV3488283

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.87, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 116 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	21.7	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 0.00102% European (non-Finnish) · 12/1,178,086 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000745% 12/1,611,350 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: CDC14B
Protein: p.Asn256Ser
Coding: c.767A>G
MANE Select: NM_033331
Type: single nucleotide variant
Location: chr9:96534106 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 81.04 · 3 PDB
Residue 256: the tyrosine-protein phosphatase domain; 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-asn256ser (accessed [today's date]).

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