Is CELA3B p.Arg28Pro (c.83G>C) pathogenic?

CELA3B p.Arg28Pro (c.83G>C) is classified Uncertain significance in CELA3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.9384); Very rare (popmax 0.000424%, nfe).

How common is CELA3B p.Arg28Pro (c.83G>C) in the general population?

CELA3B p.Arg28Pro (c.83G>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CELA3B p.Arg28Pro (c.83G>C)?

AlphaMissense predicts likely pathogenic (score 0.9384) — an in-silico prediction, not a clinical call.

CELA3B p.Arg28Pro

c.83G>C · VCV4225174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9384 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9384	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -10.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.23 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000424% European (non-Finnish) · 5/1,179,956 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,924 alleles · very rare exomes 4/1,461,788 · genomes 1/152,136 · joint denominator

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: CELA3B
Protein: p.Arg28Pro
Coding: c.83G>C
MANE Select: NM_007352
Type: single nucleotide variant
Location: chr1:21978408 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.13

Full CELA3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELA3B p.Arg131Cys Benign ★★ same type
CELA3B p.Ile63= Benign ★★ same type
CELA3B p.Ala268Thr Uncertain significance ★ ⚠ same type
CELA3B p.Ala64Thr Uncertain significance ★ ⚠ same type
CELA3B p.Arg210Cys Uncertain significance ★ ⚠ same type
CELA3B p.Arg4Gln Uncertain significance ★ ⚠ same type
CELA3B p.Arg4Gly Uncertain significance ★ ⚠ same type
CELA3B p.Arg90His 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/cela3b-p-arg28pro (accessed [today's date]).

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