Is CDC14A p.Thr31Ala (c.91A>G) pathogenic?

CDC14A p.Thr31Ala (c.91A>G) is classified Uncertain significance in CDC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-26). AlphaMissense: ambiguous (0.5589); Very rare (popmax 8.5e-05%, nfe).

How common is CDC14A p.Thr31Ala (c.91A>G) in the general population?

CDC14A p.Thr31Ala (c.91A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about CDC14A p.Thr31Ala (c.91A>G)?

AlphaMissense predicts ambiguous (score 0.5589) — an in-silico prediction, not a clinical call.

CDC14A p.Thr31Ala

c.91A>G · VCV4902613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5589	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	24.2	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 8.5e-05% European (non-Finnish) · 1/1,176,854 alleles

Overall 6.86e-05% 1/1,457,230 alleles · very rare

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.Thr31Ala
Coding: c.91A>G
MANE Select: NM_003672
Type: single nucleotide variant
Location: chr1:100353803 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 31: the 'a' region

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

Similar variants

CDC14A p.Thr31= Likely benign ★ 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-thr31ala (accessed [today's date]).

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