Is CDC14A p.Val175Ile (c.523G>A) pathogenic?

CDC14A p.Val175Ile (c.523G>A) is classified Uncertain significance in CDC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-11). AlphaMissense: likely pathogenic (0.6953); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDC14A p.Val175Ile (c.523G>A)?

CDC14A p.Val175Ile (c.523G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDC14A p.Val175Ile (c.523G>A) in the general population?

CDC14A p.Val175Ile (c.523G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC14A p.Val175Ile (c.523G>A)?

AlphaMissense predicts likely pathogenic (score 0.6953) — an in-silico prediction, not a clinical call.

CDC14A p.Val175Ile

c.523G>A · rs2524299347 · VCV2475620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6953	likely pathogenic
REVEL	0.274	benign-leaning
SaProt	LLR -11.91	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	26.1	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

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.Val175Ile
Coding: c.523G>A
MANE Select: NM_003672
dbSNP: rs2524299347
Type: single nucleotide variant
Location: chr1:100455408 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 175: a UniProt-annotated variant site (in dfnb32); the 'linker' 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-val175ile (accessed [today's date]).

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