Is CELA2A p.Ile148Val (c.442A>G) pathogenic?

CELA2A p.Ile148Val (c.442A>G) is classified Uncertain significance in CELA2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-21). AlphaMissense: likely benign (0.0787); Rare (popmax 0.186%, sas); Associated with abdominal obesity-metabolic syndrome 4.

What condition is associated with CELA2A p.Ile148Val (c.442A>G)?

CELA2A p.Ile148Val (c.442A>G) is associated with abdominal obesity-metabolic syndrome 4 (ClinVar).

How common is CELA2A p.Ile148Val (c.442A>G) in the general population?

CELA2A p.Ile148Val (c.442A>G) is rare (popmax 0.186%, sas) (gnomAD).

What do computational predictors say about CELA2A p.Ile148Val (c.442A>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

CELA2A p.Ile148Val

c.442A>G · VCV3779043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.186%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abdominal obesity-metabolic syndrome 4

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -4.36	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 0.56	GERP 0.63
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.22 · regional, not allelic
Overall
CADD	13.74	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.186% South Asian · 169/91,074 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.0109% 176/1,614,010 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.186%	539
Remaining individualsnot grpmax-eligible	0.0096%	10,416
European (non-Finnish)	8.47e-05%	1,179,947

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.Ile148Val
Coding: c.442A>G
MANE Select: NM_033440
Type: single nucleotide variant
Location: chr1:15463471 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66
Residue 148: the peptidase s1 domain

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

Disease context

abdominal obesity-metabolic syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CELA2A p.Leu85Met Likely pathogenic ★★ ⚠ same condition
CELA2A p.Thr70Met Pathogenic ★★ same condition
CELA2A p.Trp191Ter Likely pathogenic ★ same condition
CELA2A c.356+5G>C Uncertain significance ★ same condition
CELA2A p.Leu127Met Uncertain significance ★ ⚠ same condition
CELA2A c.639+1G>C Pathogenic same condition
CELA2A p.Asp121Asn Pathogenic same condition
CELA2A p.Gln230Glu Likely benign ★★ 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-ile148val (accessed [today's date]).

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