Is CDCA7 p.Leu302Val (c.904C>G) pathogenic?

CDCA7 p.Leu302Val (c.904C>G) is classified Uncertain significance in CDCA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0561%, afr).

How common is CDCA7 p.Leu302Val (c.904C>G) in the general population?

CDCA7 p.Leu302Val (c.904C>G) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

What do computational predictors say about CDCA7 p.Leu302Val (c.904C>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

CDCA7 p.Leu302Val

c.904C>G · rs113040501 · VCV1478877

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.90	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 -0.37	GERP -5.5
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L223V vs ClinVar L302V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% African / African-American · 42/74,880 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00366% 59/1,611,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,783
Remaining individualsnot grpmax-eligible	0.024%	4,158
South Asian	0.00111%	90,310
European (non-Finnish)	8.48e-05%	1,178,805

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.Leu302Val
Coding: c.904C>G
MANE Select: NM_031942
dbSNP: rs113040501
Type: single nucleotide variant
Location: chr2:173365461 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 302: an α-helix

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-leu302val (accessed [today's date]).

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