Is CDCA7 p.Leu149Ile (c.445C>A) pathogenic?

CDCA7 p.Leu149Ile (c.445C>A) is classified Uncertain significance in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely benign (0.2496); Ultra-rare (popmax 0.033%, mid).

How common is CDCA7 p.Leu149Ile (c.445C>A) in the general population?

CDCA7 p.Leu149Ile (c.445C>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CDCA7 p.Leu149Ile (c.445C>A)?

AlphaMissense predicts likely benign (score 0.2496) — an in-silico prediction, not a clinical call.

CDCA7 p.Leu149Ile

c.445C>A · rs1456932401 · VCV1897201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2496 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2496	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	25.7	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 L70I vs ClinVar L149I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000616% 9/1,461,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0048%	20,837
African / African-American	0.004%	25,013
European (non-Finnish)	8.47e-05%	1,180,036

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.Leu149Ile
Coding: c.445C>A
MANE Select: NM_031942
dbSNP: rs1456932401
Type: single nucleotide variant
Location: chr2:173363286 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 149: the 'disordered' region; the 'interaction with myc' region

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-leu149ile (accessed [today's date]).

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