Is CD2BP2 p.Ser141Leu (c.422C>T) pathogenic?

CD2BP2 p.Ser141Leu (c.422C>T) is classified Uncertain significance in CD2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0165%, mid).

How common is CD2BP2 p.Ser141Leu (c.422C>T) in the general population?

CD2BP2 p.Ser141Leu (c.422C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD2BP2 p.Ser141Leu (c.422C>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CD2BP2 p.Ser141Leu

c.422C>T · rs771942416 · VCV2211489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -9.53	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 7.3	GERP -0.94, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,693 bp · p 0.012 · regional, not allelic
Overall
CADD	22.3	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,070 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00112% 18/1,607,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,070
African / African-American	0.0107%	9,352
Admixed American	0.00334%	29,933
Remaining individualsnot grpmax-eligible	0.00161%	62,190
European (non-Finnish)	0.00051%	196,112

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.Ser141Leu
Coding: c.422C>T
MANE Select: NM_006110
dbSNP: rs771942416
Type: single nucleotide variant
Location: chr16:30353754 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04 · 10 PDB
Residue 141: the 'disordered' region

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-ser141leu (accessed [today's date]).

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