Is CREB3L1 p.Pro96Arg (c.287C>G) pathogenic?

CREB3L1 p.Pro96Arg (c.287C>G) is classified Uncertain significance in CREB3L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely pathogenic (0.7623); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CREB3L1 p.Pro96Arg (c.287C>G)?

CREB3L1 p.Pro96Arg (c.287C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CREB3L1 p.Pro96Arg (c.287C>G) in the general population?

CREB3L1 p.Pro96Arg (c.287C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREB3L1 p.Pro96Arg (c.287C>G)?

AlphaMissense predicts likely pathogenic (score 0.7623) — an in-silico prediction, not a clinical call.

CREB3L1 p.Pro96Arg

c.287C>G · VCV4006732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7623 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7623	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -8.52	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 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 33 kb · p 0.68 · regional, not allelic
Overall
CADD	26.6	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: CREB3L1
Protein: p.Pro96Arg
Coding: c.287C>G
MANE Select: NM_052854
Type: single nucleotide variant
Location: chr11:46300119 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.66
Residue 96: the 'disordered' region

Full CREB3L1 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

CREB3L1 p.Pro96= Likely benign ★ same residue
CREB3L1 p.Ala151Ser Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Arg236His Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Arg268Trp Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Arg464Trp Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Glu287Lys Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Glu477Lys Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Glu484Asp 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/creb3l1-p-pro96arg (accessed [today's date]).

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