Is CREB3L1 p.Ser362Phe (c.1085C>T) pathogenic?

CREB3L1 p.Ser362Phe (c.1085C>T) is classified Uncertain significance in CREB3L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.3374); Very rare (popmax 0.000947%, nfe).

How common is CREB3L1 p.Ser362Phe (c.1085C>T) in the general population?

CREB3L1 p.Ser362Phe (c.1085C>T) is very rare (popmax 0.000947%, nfe) (gnomAD).

What do computational predictors say about CREB3L1 p.Ser362Phe (c.1085C>T)?

AlphaMissense predicts likely benign (score 0.3374) — an in-silico prediction, not a clinical call.

CREB3L1 p.Ser362Phe

c.1085C>T · VCV4055999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000947%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3374	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense 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 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 4,422 bp · p 0.17 · regional, not allelic
Overall
CADD	28.4	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

Grpmax group 0.000947% European (non-Finnish) · 11/1,160,966 alleles

Filtering AF 0.000508% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000372%

Overall 0.000773% 11/1,423,446 alleles · very rare

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: CREB3L1
Protein: p.Ser362Phe
Coding: c.1085C>T
MANE Select: NM_052854
Type: single nucleotide variant
Location: chr11:46316339 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.66

Full CREB3L1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREB3L1 p.Ala151Ser Uncertain significance ★★ ⚠ same type
CREB3L1 p.Ala369Thr Uncertain significance ★★ ⚠ same type
CREB3L1 p.Ala95Val Uncertain significance ★★ ⚠ same type
CREB3L1 p.Arg223Cys Uncertain significance ★★ ⚠ same type
CREB3L1 p.Arg236His Uncertain significance ★★ ⚠ same type
CREB3L1 p.Arg268Trp Uncertain significance ★★ ⚠ same type
CREB3L1 p.Arg308Cys Uncertain significance ★★ ⚠ same type
CREB3L1 p.Arg462Trp 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/creb3l1-p-ser362phe (accessed [today's date]).

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