Is CDC14A p.Arg174Ter (c.520C>T) pathogenic?

CDC14A p.Arg174Ter (c.520C>T) is classified Likely pathogenic in CDC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-08). Very rare (popmax 0.00349%, amr); Associated with Rare genetic deafness.

What condition is associated with CDC14A p.Arg174Ter (c.520C>T)?

CDC14A p.Arg174Ter (c.520C>T) is associated with Rare genetic deafness (ClinVar).

How common is CDC14A p.Arg174Ter (c.520C>T) in the general population?

CDC14A p.Arg174Ter (c.520C>T) is very rare (popmax 0.00349%, amr) (gnomAD).

CDC14A p.Arg174Ter

c.520C>T · rs765155697 · VCV667367

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00349%, amr)

Conditions

Rare genetic deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00349% Admixed American · 2/57,316 alleles

Filtering AF 0.000579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000879% 14/1,593,182 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00349%	28,658
South Asian	0.00232%	43,194
African / African-American	0.00135%	74,132
European (non-Finnish)	0.00077%	129,889

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.Arg174Ter
Coding: c.520C>T
MANE Select: NM_003672
dbSNP: rs765155697
Type: single nucleotide variant
Location: chr1:100455405 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 174: 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

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

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-arg174ter (accessed [today's date]).

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