Is CDC14B p.Lys271Arg (c.812A>G) pathogenic?

CDC14B p.Lys271Arg (c.812A>G) is classified Uncertain significance in CDC14B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.0635); Very rare (popmax 8.48e-05%, nfe).

How common is CDC14B p.Lys271Arg (c.812A>G) in the general population?

CDC14B p.Lys271Arg (c.812A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDC14B p.Lys271Arg (c.812A>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

CDC14B p.Lys271Arg

c.812A>G · rs1838918146 · VCV2239064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 116 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	19.36	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 8.48e-05% European (non-Finnish) · 1/1,179,266 alleles

Overall 0.000205% 3/1,460,892 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)grpmax	8.48e-05%	1,179,266

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys271Arg
Coding: c.812A>G
MANE Select: NM_033331
dbSNP: rs1838918146
Type: single nucleotide variant
Location: chr9:96534061 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 81.04 · 3 PDB
Residue 271: 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-lys271arg (accessed [today's date]).

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