Is CD2BP2 p.Phe299Val (c.895T>G) pathogenic?

CD2BP2 p.Phe299Val (c.895T>G) is classified Uncertain significance in CD2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.9103); Ultra-rare (popmax 0.0234%, nfe).

How common is CD2BP2 p.Phe299Val (c.895T>G) in the general population?

CD2BP2 p.Phe299Val (c.895T>G) is ultra-rare (popmax 0.0234%, nfe) (gnomAD).

What do computational predictors say about CD2BP2 p.Phe299Val (c.895T>G)?

AlphaMissense predicts likely pathogenic (score 0.9103) — an in-silico prediction, not a clinical call.

CD2BP2 p.Phe299Val

c.895T>G · rs2049498212 · VCV2282361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9103 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9103	likely pathogenic
REVEL	0.579	indeterminate
SaProt	LLR -11.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,693 bp · p 0.012 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0234% European (non-Finnish) · 263/1,124,228 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0202%

Overall 0.0204% 286/1,400,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0234%	4,275
Remaining individualsnot grpmax-eligible	0.0165%	6,042
African / African-American	0.00814%	12,289
East Asian	0.00673%	14,849
South Asian	0.00334%	29,933
Finnishnot grpmax-eligible	0.00157%	63,778

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.Phe299Val
Coding: c.895T>G
MANE Select: NM_006110
dbSNP: rs2049498212
Type: single nucleotide variant
Location: chr16:30353201 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04 · 10 PDB
Residue 299: the gyf domain; a β-strand

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

Similar variants

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.Arg201Leu Uncertain significance ★ ⚠ same type
CD2BP2 p.Arg201Trp 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-phe299val (accessed [today's date]).

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