Is CDC14A p.Ser330= (c.990G>A) pathogenic?

CDC14A p.Ser330= (c.990G>A) is classified Benign in CDC14A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele.

CDC14A p.Ser330=

Q: How common is CDC14A p.Ser330= (c.990G>A) in the general population?

CDC14A p.Ser330= (c.990G>A) is common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.990G>A · rs2270694 · VCV508568

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.4	GERP -4.7
Overall
CADD	0.683	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.1% Middle Eastern · 766/5,858 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.6%

Overall 12.1% 189,505/1,562,224 alleles · common exomes 172,533/1,410,220 · genomes 16,972/152,004 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	20.7%	5
Amishnot grpmax-eligible	18.5%	5
Finnishnot grpmax-eligible	16.1%	6
Middle Easterngrpmax	13.1%	8
European (non-Finnish)	12.6%	8
Remaining individualsnot grpmax-eligible	12.1%	8
Admixed American	9.8%	10
South Asian	8.98%	11
East Asian	6.17%	16
African / African-American	5.87%	17

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser330=
Coding: c.990G>A
MANE Select: NM_003672
dbSNP: rs2270694
Type: single nucleotide variant
Location: chr1:100484304 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 330: 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

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-ser330 (accessed [today's date]).

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