Is CREBBP p.Pro704Ser (c.2110C>T) pathogenic?

CREBBP p.Pro704Ser (c.2110C>T) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with CREBBP p.Pro704Ser (c.2110C>T)?

CREBBP p.Pro704Ser (c.2110C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CREBBP p.Pro704Ser (c.2110C>T) in the general population?

CREBBP p.Pro704Ser (c.2110C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CREBBP p.Pro704Ser (c.2110C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

CREBBP p.Pro704Ser

c.2110C>T · rs757578450 · VCV2276142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.52 · regional, not allelic
Overall
CADD	24.8	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 0.00668% East Asian · 3/44,904 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,968
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,090
European (non-Finnish)	8.47e-05%	1,180,026

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: CREBBP
Protein: p.Pro704Ser
Coding: c.2110C>T
MANE Select: NM_004380
dbSNP: rs757578450
Type: single nucleotide variant
Location: chr16:3778014 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CREBBP p.Pro704= Uncertain significance ★★ same residue
CREBBP p.Arg1786Cys Pathogenic/Likely pathogenic ★★ same condition
CREBBP p.Ala1510Val Uncertain significance ★★ ⚠ same condition
CREBBP p.Ala15Gly Uncertain significance ★★ ⚠ same condition
CREBBP p.Ala1830Thr Uncertain significance ★★ ⚠ same condition
CREBBP p.Ala2049Pro Uncertain significance ★★ ⚠ same condition
CREBBP p.Ala828Val Uncertain significance ★★ ⚠ same condition
CREBBP p.Arg1960Pro Uncertain significance ★★ same condition

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-pro704ser (accessed [today's date]).

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