Is CELA2A p.Ala35Val (c.104C>T) pathogenic?

CELA2A p.Ala35Val (c.104C>T) is classified Uncertain significance in CELA2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: ambiguous (0.3473); Ultra-rare (popmax 0.0312%, eas).

How common is CELA2A p.Ala35Val (c.104C>T) in the general population?

CELA2A p.Ala35Val (c.104C>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CELA2A p.Ala35Val (c.104C>T)?

AlphaMissense predicts ambiguous (score 0.3473) — an in-silico prediction, not a clinical call.

CELA2A p.Ala35Val

c.104C>T · rs147042451 · VCV2515678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3473 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Computational evidence

Protein change
AlphaMissense	0.3473	ambiguous
REVEL	0.301	indeterminate
SaProt	LLR -9.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.7
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.22 · regional, not allelic
Overall
CADD	5.458	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 0.0312% East Asian · 14/44,890 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00273% 44/1,614,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
South Asian	0.0143%	7,006
Admixed American	0.00167%	60,024
European (non-Finnish)	0.00136%	73,751

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.Ala35Val
Coding: c.104C>T
MANE Select: NM_033440
dbSNP: rs147042451
Type: single nucleotide variant
Location: chr1:15457149 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66
Residue 35: the peptidase s1 domain

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

Similar variants

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
CELA2A p.Ala184Gly 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-ala35val (accessed [today's date]).

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