Is CREBBP p.Arg2004Ter (c.6010C>T) pathogenic?

CREBBP p.Arg2004Ter (c.6010C>T) is classified Pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-15). Absent from gnomAD v4.1.

How common is CREBBP p.Arg2004Ter (c.6010C>T) in the general population?

CREBBP p.Arg2004Ter (c.6010C>T) is absent from gnomAD v4.1 (gnomAD).

CREBBP p.Arg2004Ter

c.6010C>T · rs886039331 · VCV265084

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,130)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (31 of 31) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,130). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CREBBP
Protein: p.Arg2004Ter
Coding: c.6010C>T
MANE Select: NM_004380
dbSNP: rs886039331
Type: single nucleotide variant
Location: chr16:3729037 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2004: the 'disordered' region

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

Similar variants

CREBBP p.Arg2004Gln Uncertain significance ⚠ same residue
CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3369+1G>T Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3779+1G>A Pathogenic ★★ same type
CREBBP c.3779+1G>T Pathogenic ★★ same type
CREBBP c.3836+1G>A Pathogenic ★★ same type
CREBBP c.3914+3G>T Likely pathogenic ★★ 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/crebbp-p-arg2004ter (accessed [today's date]).

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