Is CELA3B p.Val239Phe (c.715G>T) pathogenic?

CELA3B p.Val239Phe (c.715G>T) is classified Uncertain significance in CELA3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.7794); Very rare (popmax 0.00314%, nfe).

How common is CELA3B p.Val239Phe (c.715G>T) in the general population?

CELA3B p.Val239Phe (c.715G>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about CELA3B p.Val239Phe (c.715G>T)?

AlphaMissense predicts likely pathogenic (score 0.7794) — an in-silico prediction, not a clinical call.

CELA3B p.Val239Phe

c.715G>T · VCV4651847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7794	likely pathogenic
REVEL	0.364	indeterminate
SaProt	LLR -13.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.23 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00314% European (non-Finnish) · 37/1,180,022 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00248% 40/1,614,064 alleles · very rare exomes 37/1,461,878 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,016
South Asian	0.0011%	91,066

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.Val239Phe
Coding: c.715G>T
MANE Select: NM_007352
Type: single nucleotide variant
Location: chr1:21986603 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.13
Residue 239: the peptidase s1 domain

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-val239phe (accessed [today's date]).

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