Is CDC16 p.Phe205Ser (c.614T>C) pathogenic?

CDC16 p.Phe205Ser (c.614T>C) is classified Uncertain significance in CDC16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.9041); Very rare (popmax 0.00897%, eas).

How common is CDC16 p.Phe205Ser (c.614T>C) in the general population?

CDC16 p.Phe205Ser (c.614T>C) is very rare (popmax 0.00897%, eas) (gnomAD).

What do computational predictors say about CDC16 p.Phe205Ser (c.614T>C)?

AlphaMissense predicts likely pathogenic (score 0.9041) — an in-silico prediction, not a clinical call.

CDC16 p.Phe205Ser

c.614T>C · VCV4223168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00897%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9041	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -11.80	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 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 0.00031 · regional, not allelic
Overall
CADD	24.3	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 0.00897% East Asian · 4/44,594 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.000319% 5/1,565,024 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00897%	11,148
African / African-American	0.00135%	73,918

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: CDC16
Protein: p.Phe205Ser
Coding: c.614T>C
MANE Select: NM_001078645
Type: single nucleotide variant
Location: chr13:114243329 (GRCh38)
Gene constraint: LOEUF 0.657 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 21 PDB
Residue 205: an α-helix

Full CDC16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC16 p.Ile132= Benign ★★ same type
CDC16 p.Ala142Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala319Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala44Gly Uncertain significance ★ ⚠ same type
CDC16 p.Ala479Ser Uncertain significance ★ ⚠ same type
CDC16 p.Ala51Thr Uncertain significance ★ ⚠ same type
CDC16 p.Ala536Ser Uncertain significance ★ ⚠ same type
CDC16 p.Ala57Thr 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/cdc16-p-phe205ser (accessed [today's date]).

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