Is CREBBP p.Ser78Arg (c.234C>A) pathogenic?

CREBBP p.Ser78Arg (c.234C>A) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). AlphaMissense: likely pathogenic (0.8131); Absent from gnomAD v4.1.

How common is CREBBP p.Ser78Arg (c.234C>A) in the general population?

CREBBP p.Ser78Arg (c.234C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Ser78Arg (c.234C>A)?

AlphaMissense predicts likely pathogenic (score 0.8131) — an in-silico prediction, not a clinical call.

CREBBP p.Ser78Arg

c.234C>A · rs145925174 · VCV1326380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8131 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8131	likely pathogenic
REVEL	0.378	indeterminate
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -5.5, phastCons 0.029
Regional constraint	o/e 1.05	unconstrained · MANE · 69 kb · p 0.4 · regional, not allelic
Overall
CADD	16.53	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CREBBP
Protein: p.Ser78Arg
Coding: c.234C>A
MANE Select: NM_004380
dbSNP: rs145925174
Type: single nucleotide variant
Location: chr16:3850861 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 78: the 'disordered' region

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

Similar variants

CREBBP p.Ser78= Likely benign ★★ 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-ser78arg (accessed [today's date]).

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