Is CDC14A p.Ile364Val (c.1090A>G) pathogenic?

CDC14A p.Ile364Val (c.1090A>G) is classified Benign/Likely benign in CDC14A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-27). AlphaMissense: likely benign (0.0898); Rare (popmax 0.386%, sas).

How common is CDC14A p.Ile364Val (c.1090A>G) in the general population?

CDC14A p.Ile364Val (c.1090A>G) is rare (popmax 0.386%, sas) (gnomAD).

What do computational predictors say about CDC14A p.Ile364Val (c.1090A>G)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

CDC14A p.Ile364Val

c.1090A>G · rs140849467 · VCV681875

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.386%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	17.56	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 0.386% South Asian · 347/89,800 alleles

Filtering AF 0.353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.34%

Overall 0.0914% 1,470/1,607,846 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.386%	259
Middle Eastern	0.382%	262
Finnishnot grpmax-eligible	0.249%	402
Remaining individualsnot grpmax-eligible	0.12%	830
Admixed American	0.0778%	1,285
European (non-Finnish)	0.0685%	1,461
African / African-American	0.0174%	5,743
East Asian	0.00225%	44,486

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.Ile364Val
Coding: c.1090A>G
MANE Select: NM_003672
dbSNP: rs140849467
Type: single nucleotide variant
Location: chr1:100484404 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 364: a UniProt-annotated variant site (in dfnb32)

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-ile364val (accessed [today's date]).

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