Is CDC14A p.Arg406Lys (c.1217G>A) pathogenic?

CDC14A p.Arg406Lys (c.1217G>A) is classified Conflicting classifications of pathogenicity in CDC14A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-11). AlphaMissense: likely pathogenic (0.6138); Ultra-rare (popmax 0.0934%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDC14A p.Arg406Lys (c.1217G>A)?

CDC14A p.Arg406Lys (c.1217G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDC14A p.Arg406Lys (c.1217G>A) in the general population?

CDC14A p.Arg406Lys (c.1217G>A) is ultra-rare (popmax 0.0934%, amr) (gnomAD).

What do computational predictors say about CDC14A p.Arg406Lys (c.1217G>A)?

AlphaMissense predicts likely pathogenic (score 0.6138) — an in-silico prediction, not a clinical call.

CDC14A p.Arg406Lys

c.1217G>A · rs748922639 · VCV1181232

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6138 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0934%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6138	likely pathogenic
REVEL	0.196	benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	26.3	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 0.0934% Admixed American · 56/59,980 alleles

Filtering AF 0.0738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.00409% 66/1,611,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0934%	1,071
Remaining individualsnot grpmax-eligible	0.00961%	10,403
European (non-Finnish)	0.000339%	294,553

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.Arg406Lys
Coding: c.1217G>A
MANE Select: NM_003672
dbSNP: rs748922639
Type: single nucleotide variant
Location: chr1:100494897 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 406: a UniProt-annotated variant site (in dfnb32); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC14A p.Ala211Gly Uncertain significance ★★ ⚠ same condition
CDC14A p.Ala482Thr Uncertain significance ★★ ⚠ same condition
CDC14A p.Arg261Gln Uncertain significance ★★ ⚠ same condition
CDC14A p.Arg376Gln Uncertain significance ★★ ⚠ same condition
CDC14A p.Cys12Tyr Uncertain significance ★★ ⚠ same condition
CDC14A p.Glu271Lys Uncertain significance ★★ ⚠ same condition
CDC14A p.Gly283Ala Uncertain significance ★★ ⚠ same condition
CDC14A p.Gly423Glu Uncertain significance ★★ ⚠ same condition

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-arg406lys (accessed [today's date]).

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