Is CDCA2 p.Tyr206Ser (c.617A>C) pathogenic?

CDCA2 p.Tyr206Ser (c.617A>C) is classified Likely benign in CDCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0633); Very rare (popmax 0.0022%, sas).

How common is CDCA2 p.Tyr206Ser (c.617A>C) in the general population?

CDCA2 p.Tyr206Ser (c.617A>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CDCA2 p.Tyr206Ser (c.617A>C)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

CDCA2 p.Tyr206Ser

c.617A>C · rs991221398 · VCV2243378

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.03	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 -0.15	GERP -5.3
Regional constraint	o/e 1.04	unconstrained · MANE · 47 kb · p 0.15 · regional, not allelic
Overall
CADD	0.038	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 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,461,790 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.00017%	589,971

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: CDCA2
Protein: p.Tyr206Ser
Coding: c.617A>C
MANE Select: NM_152562
dbSNP: rs991221398
Type: single nucleotide variant
Location: chr8:25468295 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.61 · 4 PDB

Full CDCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA2 p.Val467Ile Uncertain significance ★★ ⚠ same type
CDCA2 p.Lys754Thr Benign ★★ same type
CDCA2 p.Ser291= Benign ★★ same type
CDCA2 p.Thr50Ile Benign ★★ same type
CDCA2 p.Ala187Thr Uncertain significance ★ ⚠ same type
CDCA2 p.Ala217Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala23Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala92Gly 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/cdca2-p-tyr206ser (accessed [today's date]).

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