Is CDCA7 p.Arg241Cys (c.721C>T) pathogenic?

CDCA7 p.Arg241Cys (c.721C>T) is classified Uncertain significance in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-06). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.00225%, eas).

How common is CDCA7 p.Arg241Cys (c.721C>T) in the general population?

CDCA7 p.Arg241Cys (c.721C>T) is very rare (popmax 0.00225%, eas) (gnomAD).

What do computational predictors say about CDCA7 p.Arg241Cys (c.721C>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

CDCA7 p.Arg241Cys

c.721C>T · rs1328294188 · VCV1372353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -8.99	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	23.8	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 R162C vs ClinVar R241C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% East Asian · 1/44,500 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,456,540 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00225%	44,500
European (non-Finnish)	0.00017%	589,181

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.Arg241Cys
Coding: c.721C>T
MANE Select: NM_031942
dbSNP: rs1328294188
Type: single nucleotide variant
Location: chr2:173364816 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 241: an α-helix

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

Similar variants

CDCA7 p.Arg241Gly Uncertain significance ★ ⚠ same residue
CDCA7 p.Arg241His Uncertain significance ★ ⚠ 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.Arg171Cys 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-arg241cys (accessed [today's date]).

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