Is CDC14A p.Arg312Pro (c.935G>C) pathogenic?

CDC14A p.Arg312Pro (c.935G>C) is classified Uncertain significance in CDC14A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-24). AlphaMissense: likely pathogenic (0.999); Very rare (popmax 0.00223%, eas).

How common is CDC14A p.Arg312Pro (c.935G>C) in the general population?

CDC14A p.Arg312Pro (c.935G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDC14A p.Arg312Pro (c.935G>C)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

CDC14A p.Arg312Pro

c.935G>C · rs369245990 · VCV2044884

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 5% in CDC14A
REVEL	0.677	pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.011 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00223% East Asian · 1/44,844 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,613,018 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,844
European (non-Finnish)	0.000848%	117,965

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.Arg312Pro
Coding: c.935G>C
MANE Select: NM_003672
dbSNP: rs369245990
Type: single nucleotide variant
Location: chr1:100468052 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.77
Residue 312: 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.Arg312Gln Pathogenic/Likely pathogenic ★★ same residue
CDC14A p.Arg312Gly Pathogenic/Likely pathogenic ★★ same residue
CDC14A p.Arg261Ter 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-arg312pro (accessed [today's date]).

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