Is CDC14B p.Asn93Ser (c.278A>G) pathogenic?

CDC14B p.Asn93Ser (c.278A>G) is classified Uncertain significance in CDC14B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.2529); Ultra-rare (popmax 0.0165%, mid).

How common is CDC14B p.Asn93Ser (c.278A>G) in the general population?

CDC14B p.Asn93Ser (c.278A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CDC14B p.Asn93Ser (c.278A>G)?

AlphaMissense predicts likely benign (score 0.2529) — an in-silico prediction, not a clinical call.

CDC14B p.Asn93Ser

c.278A>G · VCV3488282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2529	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.13, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 116 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	24.7	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 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000275% 4/1,452,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
South Asian	0.00112%	89,652
European (non-Finnish)	0.00017%	587,748

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.Asn93Ser
Coding: c.278A>G
MANE Select: NM_033331
Type: single nucleotide variant
Location: chr9:96564826 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 81.04 · 3 PDB
Residue 93: an α-helix; the 'a' 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-asn93ser (accessed [today's date]).

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