Is CDC14A p.Pro196Ser (c.586C>T) pathogenic?

CDC14A p.Pro196Ser (c.586C>T) is classified Uncertain significance in CDC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.3524); Very rare (popmax 0.00435%, nfe).

How common is CDC14A p.Pro196Ser (c.586C>T) in the general population?

CDC14A p.Pro196Ser (c.586C>T) is very rare (popmax 0.00435%, nfe) (gnomAD).

What do computational predictors say about CDC14A p.Pro196Ser (c.586C>T)?

AlphaMissense predicts ambiguous (score 0.3524) — an in-silico prediction, not a clinical call.

CDC14A p.Pro196Ser

c.586C>T · rs755291422 · VCV1448360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3524	ambiguous
REVEL	0.25	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 0.23, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	24.0	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 0.00435% European (non-Finnish) · 51/1,171,258 alleles

Filtering AF 0.00336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00304%

Overall 0.00346% 55/1,589,910 alleles · very rare exomes 52/1,437,836 · genomes 3/152,074 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00435%	22,966
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,204
Remaining individualsnot grpmax-eligible	0.00325%	30,756
Admixed American	0.00181%	55,126

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: CDC14A
Protein: p.Pro196Ser
Coding: c.586C>T
MANE Select: NM_003672
dbSNP: rs755291422
Type: single nucleotide variant
Location: chr1:100455471 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 196: the tyrosine-protein phosphatase domain; a UniProt-annotated variant site (in dfnb32); the 'b' region

Full CDC14A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC14A p.Pro196Ala Uncertain significance ★ ⚠ same residue
CDC14A p.Arg261Ter Pathogenic ★★ same type
CDC14A p.Arg312Gln Pathogenic/Likely pathogenic ★★ same type
CDC14A p.Arg312Gly Pathogenic/Likely pathogenic ★★ same type
CDC14A p.Arg339Ter Pathogenic ★★ same type
CDC14A p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
CDC14A p.Arg376Ter Pathogenic/Likely pathogenic ★★ same type
CDC14A p.Ala211Gly 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/cdc14a-p-pro196ser (accessed [today's date]).

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