Is CELA2B p.Ala35Val (c.104C>T) pathogenic?

CELA2B p.Ala35Val (c.104C>T) is classified Likely benign in CELA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: ambiguous (0.3856); Ultra-rare (popmax 0.015%, amr).

How common is CELA2B p.Ala35Val (c.104C>T) in the general population?

CELA2B p.Ala35Val (c.104C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CELA2B p.Ala35Val (c.104C>T)?

AlphaMissense predicts ambiguous (score 0.3856) — an in-silico prediction, not a clinical call.

CELA2B p.Ala35Val

c.104C>T · rs150801399 · VCV2388139

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Computational evidence

Protein change
AlphaMissense	0.3856	ambiguous
REVEL	0.445	indeterminate
SaProt	LLR -9.61	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.68 · regional, not allelic
Overall
CADD	7.256	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 0.015% Admixed American · 9/59,982 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.0105% 170/1,613,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,665
European (non-Finnish)	0.0131%	7,613
African / African-American	0.00534%	18,724
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Ala35Val
Coding: c.104C>T
MANE Select: NM_015849
dbSNP: rs150801399
Type: single nucleotide variant
Location: chr1:15476520 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.37
Residue 35: 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-ala35val (accessed [today's date]).

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