Is CDCA8 p.Val50Met (c.148G>A) pathogenic?

CDCA8 p.Val50Met (c.148G>A) is classified Likely benign in CDCA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1099); Very rare (popmax 0.00833%, amr).

How common is CDCA8 p.Val50Met (c.148G>A) in the general population?

CDCA8 p.Val50Met (c.148G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CDCA8 p.Val50Met (c.148G>A)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

CDCA8 p.Val50Met

c.148G>A · VCV4650968

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.41	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 2	GERP -0.079, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 0.00025 · regional, not allelic
Overall
CADD	16.84	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 0.00833% Admixed American · 5/60,000 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
East Asian	0.00446%	22,446

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: CDCA8
Protein: p.Val50Met
Coding: c.148G>A
MANE Select: NM_001256875
Type: single nucleotide variant
Location: chr1:37692958 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.28 · 15 PDB
Residue 50: the 'required for interaction with senp3' region; the 'required for centromere localization' region; the 'required for interaction with incenp' region; the 'required to form a minimal cpc core complex that localizes to the central spindle and midbody and properly executes the role of the cpc during cytokinesis' region; an α-helix; the 'required for interaction with incenp and birc5' region

Full CDCA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA8 p.Ala140Val Uncertain significance ★ ⚠ same type
CDCA8 p.Ala173Val Uncertain significance ★ ⚠ same type
CDCA8 p.Arg166Cys Uncertain significance ★ ⚠ same type
CDCA8 p.Arg176Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg210Trp Uncertain significance ★ ⚠ same type
CDCA8 p.Arg240Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg277Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg35Gln 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/cdca8-p-val50met (accessed [today's date]).

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