Is CD2BP2 p.Arg201Trp (c.601C>T) pathogenic?

CD2BP2 p.Arg201Trp (c.601C>T) is classified Uncertain significance in CD2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.1279); Ultra-rare (popmax 0.0153%, nfe).

How common is CD2BP2 p.Arg201Trp (c.601C>T) in the general population?

CD2BP2 p.Arg201Trp (c.601C>T) is ultra-rare (popmax 0.0153%, nfe) (gnomAD).

What do computational predictors say about CD2BP2 p.Arg201Trp (c.601C>T)?

AlphaMissense predicts likely benign (score 0.1279) — an in-silico prediction, not a clinical call.

CD2BP2 p.Arg201Trp

c.601C>T · rs199947984 · VCV2253201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1279 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1279	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,693 bp · p 0.012 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0153% European (non-Finnish) · 181/1,179,988 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0118% 190/1,613,972 alleles · ultra-rare exomes 176/1,461,788 · genomes 14/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0153%	6,519
Remaining individualsnot grpmax-eligible	0.008%	12,496
East Asian	0.00445%	22,447
African / African-American	0.00267%	37,460

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: CD2BP2
Protein: p.Arg201Trp
Coding: c.601C>T
MANE Select: NM_006110
dbSNP: rs199947984
Type: single nucleotide variant
Location: chr16:30353575 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04 · 10 PDB
Residue 201: an α-helix

Full CD2BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2BP2 p.Arg201Leu Uncertain significance ★ ⚠ same residue
CD2BP2 p.Ala256Val Uncertain significance ★ ⚠ same type
CD2BP2 p.Ala67Val Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg129Gln Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg177Gly Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg181Gln Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg187Lys Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg224Trp 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/cd2bp2-p-arg201trp (accessed [today's date]).

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