Is CDCA7 p.Val293Met (c.877G>A) pathogenic?

CDCA7 p.Val293Met (c.877G>A) is classified Conflicting classifications of pathogenicity in CDCA7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0585); Ultra-rare (popmax 0.0479%, sas).

How common is CDCA7 p.Val293Met (c.877G>A) in the general population?

CDCA7 p.Val293Met (c.877G>A) is ultra-rare (popmax 0.0479%, sas) (gnomAD).

What do computational predictors say about CDCA7 p.Val293Met (c.877G>A)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

CDCA7 p.Val293Met

c.877G>A · rs765939337 · VCV2142547

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0479%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.37	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 -1.9	GERP -5.3
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	1.121	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V214M vs ClinVar V293M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0479% South Asian · 41/85,554 alleles

Filtering AF 0.0362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0322%

Overall 0.00431% 68/1,579,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0479%	2,087
Remaining individualsnot grpmax-eligible	0.00327%	30,587
African / African-American	0.00275%	36,380
European (non-Finnish)	0.00197%	50,787

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: CDCA7
Protein: p.Val293Met
Coding: c.877G>A
MANE Select: NM_031942
dbSNP: rs765939337
Type: single nucleotide variant
Location: chr2:173364972 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 293: a turn

Full CDCA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA7 c.384+2T>C Uncertain significance ★★ same type
CDCA7 p.Ala157Val Uncertain significance ★★ ⚠ same type
CDCA7 p.Ala391Gly Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg134Leu Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg134Trp Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg171Cys Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg171Leu Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg239Gln 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/cdca7-p-val293met (accessed [today's date]).

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