Is CDCA7 p.Arg171Leu (c.512G>T) pathogenic?

CDCA7 p.Arg171Leu (c.512G>T) is classified Uncertain significance in CDCA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-30). AlphaMissense: likely benign (0.072); Very rare (popmax 0.00178%, nfe).

How common is CDCA7 p.Arg171Leu (c.512G>T) in the general population?

CDCA7 p.Arg171Leu (c.512G>T) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about CDCA7 p.Arg171Leu (c.512G>T)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

CDCA7 p.Arg171Leu

c.512G>T · rs1686660018 · VCV2556302

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.32	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 1.8	GERP -2, phastCons 0.003
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	15.03	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 R92L vs ClinVar R171L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,026 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00157% 23/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,192
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,078

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.Arg171Leu
Coding: c.512G>T
MANE Select: NM_031942
dbSNP: rs1686660018
Type: single nucleotide variant
Location: chr2:173363353 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 171: the 'disordered' region

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

Similar variants

CDCA7 p.Arg171Cys Uncertain significance ★★ ⚠ same residue
CDCA7 p.Arg171= Likely benign ★★ same residue
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.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-arg171leu (accessed [today's date]).

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