Is CD2BP2 p.Ser203Phe (c.608C>T) pathogenic?

CD2BP2 p.Ser203Phe (c.608C>T) is classified Uncertain significance in CD2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). AlphaMissense: likely pathogenic (0.7825); Very rare (popmax 0.00167%, amr).

How common is CD2BP2 p.Ser203Phe (c.608C>T) in the general population?

CD2BP2 p.Ser203Phe (c.608C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD2BP2 p.Ser203Phe (c.608C>T)?

AlphaMissense predicts likely pathogenic (score 0.7825) — an in-silico prediction, not a clinical call.

CD2BP2 p.Ser203Phe

c.608C>T · VCV3264803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7825	likely pathogenic
REVEL	0.185	benign-leaning
SaProt	LLR -10.92	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.37, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,693 bp · p 0.012 · regional, not allelic
Overall
CADD	22.7	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 0.00167% Admixed American · 1/60,028 alleles

Overall 6.84e-05% 1/1,461,840 alleles · very rare

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.Ser203Phe
Coding: c.608C>T
MANE Select: NM_006110
Type: single nucleotide variant
Location: chr16:30353568 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04 · 10 PDB
Residue 203: an α-helix

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-ser203phe (accessed [today's date]).

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