Is CELA2A p.Arg228Gln (c.683G>A) pathogenic?

CELA2A p.Arg228Gln (c.683G>A) is classified Likely benign in CELA2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1195); Rare (popmax 0.169%, afr).

How common is CELA2A p.Arg228Gln (c.683G>A) in the general population?

CELA2A p.Arg228Gln (c.683G>A) is rare (popmax 0.169%, afr) (gnomAD).

What do computational predictors say about CELA2A p.Arg228Gln (c.683G>A)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

CELA2A p.Arg228Gln

c.683G>A · rs139163441 · VCV3141913

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -9.32	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 -2.6	GERP -4.3
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.22 · regional, not allelic
Overall
CADD	2.877	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 0.169% African / African-American · 127/75,066 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.0103% 166/1,613,988 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.169%	591
Admixed American	0.015%	6,670
Remaining individualsnot grpmax-eligible	0.0128%	7,813
South Asian	0.0121%	8,280
East Asian	0.00223%	44,880
European (non-Finnish)	0.000847%	118,003

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: CELA2A
Protein: p.Arg228Gln
Coding: c.683G>A
MANE Select: NM_033440
dbSNP: rs139163441
Type: single nucleotide variant
Location: chr1:15467429 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66
Residue 228: a disulfide bond; the peptidase s1 domain

Full CELA2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELA2A p.Arg228Trp Uncertain significance ★ ⚠ same residue
CELA2A p.Leu85Met Likely pathogenic ★★ ⚠ same type
CELA2A p.Thr70Met Pathogenic ★★ same type
CELA2A p.Gln230Glu Likely benign ★★ same type
CELA2A p.Trp191Ter Likely pathogenic ★ same type
CELA2A c.356+5G>C Uncertain significance ★ same type
CELA2A p.Ala123Thr Uncertain significance ★ same type
CELA2A p.Ala145Val 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/cela2a-p-arg228gln (accessed [today's date]).

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