Is CELA3B p.Pro101Arg (c.302C>G) pathogenic?

CELA3B p.Pro101Arg (c.302C>G) is classified Uncertain significance in CELA3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.00667%, amr).

How common is CELA3B p.Pro101Arg (c.302C>G) in the general population?

CELA3B p.Pro101Arg (c.302C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CELA3B p.Pro101Arg (c.302C>G)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

CELA3B p.Pro101Arg

c.302C>G · VCV3265716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.474	indeterminate
SaProt	LLR -10.23	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 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.23 · regional, not allelic
Overall
CADD	21.0	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 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000744% 12/1,613,256 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,000
European (non-Finnish)	0.000678%	147,504

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.Pro101Arg
Coding: c.302C>G
MANE Select: NM_007352
Type: single nucleotide variant
Location: chr1:21981112 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.13
Residue 101: the peptidase s1 domain

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.Arg28Pro Uncertain significance ★ ⚠ same type
CELA3B p.Arg4Gln Uncertain significance ★ ⚠ same type
CELA3B p.Arg4Gly 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-pro101arg (accessed [today's date]).

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