Is CDC14A p.Ala11Thr (c.31G>A) pathogenic?

CDC14A p.Ala11Thr (c.31G>A) is classified Conflicting classifications of pathogenicity in CDC14A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.8464); Rare (popmax 0.196%, afr).

How common is CDC14A p.Ala11Thr (c.31G>A) in the general population?

CDC14A p.Ala11Thr (c.31G>A) is rare (popmax 0.196%, afr) (gnomAD).

What do computational predictors say about CDC14A p.Ala11Thr (c.31G>A)?

AlphaMissense predicts likely pathogenic (score 0.8464) — an in-silico prediction, not a clinical call.

CDC14A p.Ala11Thr

c.31G>A · rs140623300 · VCV1120113

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8464 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.196%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8464	likely pathogenic
REVEL	0.037	moderately benign-leaning
SaProt	LLR -11.25	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP -0.89, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	24.3	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 0.196% African / African-American · 147/75,056 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.0115% 186/1,614,110 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.196%	511
Remaining individualsnot grpmax-eligible	0.0368%	2,717
Admixed American	0.0167%	6,003
South Asian	0.00439%	22,767
European (non-Finnish)	0.000169%	590,016

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.Ala11Thr
Coding: c.31G>A
MANE Select: NM_003672
dbSNP: rs140623300
Type: single nucleotide variant
Location: chr1:100352985 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 11: the 'a' region

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

Similar variants

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
CDC14A p.Ala482Thr 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-ala11thr (accessed [today's date]).

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