Is CELA3B p.Ser16Ala (c.46T>G) pathogenic?

CELA3B p.Ser16Ala (c.46T>G) is classified Uncertain significance in CELA3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0665); Ultra-rare (popmax 0.024%, afr).

How common is CELA3B p.Ser16Ala (c.46T>G) in the general population?

CELA3B p.Ser16Ala (c.46T>G) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about CELA3B p.Ser16Ala (c.46T>G)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

CELA3B p.Ser16Ala

c.46T>G · VCV3489984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 0.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.23 · regional, not allelic
Overall
CADD	18.11	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 0.024% African / African-American · 18/74,942 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00124% 20/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,163
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Ser16Ala
Coding: c.46T>G
MANE Select: NM_007352
Type: single nucleotide variant
Location: chr1:21978371 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.13

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-ser16ala (accessed [today's date]).

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