Is CELA2B p.Ser39Cys (c.115A>T) pathogenic?

CELA2B p.Ser39Cys (c.115A>T) is classified Uncertain significance in CELA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: ambiguous (0.5461); Very rare (popmax 0.00314%, nfe).

How common is CELA2B p.Ser39Cys (c.115A>T) in the general population?

CELA2B p.Ser39Cys (c.115A>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about CELA2B p.Ser39Cys (c.115A>T)?

AlphaMissense predicts ambiguous (score 0.5461) — an in-silico prediction, not a clinical call.

CELA2B p.Ser39Cys

c.115A>T · VCV4000089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5461	ambiguous
REVEL	0.582	indeterminate
SaProt	LLR -13.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.68 · regional, not allelic
Overall
CADD	24.0	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 0.00314% European (non-Finnish) · 37/1,180,032 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00229% 37/1,613,780 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: CELA2B
Protein: p.Ser39Cys
Coding: c.115A>T
MANE Select: NM_015849
Type: single nucleotide variant
Location: chr1:15476531 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.37
Residue 39: the peptidase s1 domain

Full CELA2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELA2B p.His232= Benign ★★ same type
CELA2B p.Ala128Thr Uncertain significance ★ ⚠ same type
CELA2B p.Ala14Val Uncertain significance ★ ⚠ same type
CELA2B p.Ala203Pro Uncertain significance ★ ⚠ same type
CELA2B p.Arg228Trp Uncertain significance ★ same type
CELA2B p.Asn129Lys Uncertain significance ★ ⚠ same type
CELA2B p.Asp226Val Uncertain significance ★ same type
CELA2B p.Asp25Val 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/cela2b-p-ser39cys (accessed [today's date]).

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