Is CDC16 p.Glu85Asp (c.255G>T) pathogenic?

CDC16 p.Glu85Asp (c.255G>T) is classified Uncertain significance in CDC16 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: ambiguous (0.5229); Very rare (popmax 0.00669%, amr).

How common is CDC16 p.Glu85Asp (c.255G>T) in the general population?

CDC16 p.Glu85Asp (c.255G>T) is very rare (popmax 0.00669%, amr) (gnomAD).

What do computational predictors say about CDC16 p.Glu85Asp (c.255G>T)?

AlphaMissense predicts ambiguous (score 0.5229) — an in-silico prediction, not a clinical call.

CDC16 p.Glu85Asp

c.255G>T · rs370232617 · VCV2241965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5229	ambiguous
REVEL	0.139	moderately benign-leaning
SaProt	LLR -8.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.027	GERP -2.8, phastCons 0.05
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 0.00031 · regional, not allelic
Overall
CADD	16.91	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 0.00669% Admixed American · 4/59,762 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000436% 7/1,606,752 alleles · very rare exomes 7/1,454,450 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00669%	14,940
European (non-Finnish)	0.000256%	391,380

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.Glu85Asp
Coding: c.255G>T
MANE Select: NM_001078645
dbSNP: rs370232617
Type: single nucleotide variant
Location: chr13:114239364 (GRCh38)
Gene constraint: LOEUF 0.657 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 21 PDB

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-glu85asp (accessed [today's date]).

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