Is CREB3 p.Ile150Thr (c.449T>C) pathogenic?

CREB3 p.Ile150Thr (c.449T>C) is classified Uncertain significance in CREB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.3137); Ultra-rare (popmax 0.0134%, eas).

How common is CREB3 p.Ile150Thr (c.449T>C) in the general population?

CREB3 p.Ile150Thr (c.449T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CREB3 p.Ile150Thr (c.449T>C)?

AlphaMissense predicts likely benign (score 0.3137) — an in-silico prediction, not a clinical call.

CREB3 p.Ile150Thr

c.449T>C · rs762841933 · VCV2250591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3137 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3137	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.08	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 1.9	GERP 0.68, phastCons 1
Overall
CADD	16.98	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 0.0134% East Asian · 6/44,828 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000625% 10/1,600,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,471
Admixed American	0.0018%	55,412
Remaining individualsnot grpmax-eligible	0.00161%	61,970
European (non-Finnish)	0.00017%	588,474

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: CREB3
Protein: p.Ile150Thr
Coding: c.449T>C
MANE Select: NM_001255978 · reported on NM_006368
dbSNP: rs762841933
Type: single nucleotide variant
Location: chr9:35735122 (GRCh38)
Structure: AlphaFold pLDDT 61.56

Full CREB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREB3 c.697-5T>C Benign ★★ same type
CREB3 p.Asn222= Benign ★★ same type
CREB3 p.Ala113Val Uncertain significance ★ ⚠ same type
CREB3 p.Arg153Cys Uncertain significance ★ ⚠ same type
CREB3 p.Arg155Pro Uncertain significance ★ ⚠ same type
CREB3 p.Arg155Trp Uncertain significance ★ ⚠ same type
CREB3 p.Arg168Cys Uncertain significance ★ ⚠ same type
CREB3 p.Arg264Cys 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/creb3-p-ile150thr (accessed [today's date]).

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