Is CDC14A p.Phe249Leu (c.747C>A) pathogenic?

CDC14A p.Phe249Leu (c.747C>A) is classified Uncertain significance in CDC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDC14A p.Phe249Leu (c.747C>A)?

CDC14A p.Phe249Leu (c.747C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDC14A p.Phe249Leu (c.747C>A) in the general population?

CDC14A p.Phe249Leu (c.747C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC14A p.Phe249Leu (c.747C>A)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

CDC14A p.Phe249Leu

c.747C>A · VCV4223152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic · top 5% in CDC14A
REVEL	0.378	indeterminate
SaProt	LLR -14.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 0.49, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC14A
Protein: p.Phe249Leu
Coding: c.747C>A
MANE Select: NM_003672
Type: single nucleotide variant
Location: chr1:100462790 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 249: 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

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-phe249leu (accessed [today's date]).

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