Is CELA2B p.Val157Phe (c.469G>T) pathogenic?

CELA2B p.Val157Phe (c.469G>T) is classified Uncertain significance in CELA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: ambiguous (0.4933); Very rare (popmax 0.00195%, nfe).

How common is CELA2B p.Val157Phe (c.469G>T) in the general population?

CELA2B p.Val157Phe (c.469G>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about CELA2B p.Val157Phe (c.469G>T)?

AlphaMissense predicts ambiguous (score 0.4933) — an in-silico prediction, not a clinical call.

CELA2B p.Val157Phe

c.469G>T · VCV4000095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4933	ambiguous
REVEL	0.702	pathogenic-leaning
SaProt	LLR -8.23	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP -2.6, phastCons 0.23
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.68 · regional, not allelic
Overall
CADD	22.6	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 0.00195% European (non-Finnish) · 23/1,179,942 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00149% 24/1,613,908 alleles · very rare exomes 23/1,461,712 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,302
African / African-American	0.00133%	74,926

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.Val157Phe
Coding: c.469G>T
MANE Select: NM_015849
Type: single nucleotide variant
Location: chr1:15483376 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.37
Residue 157: 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-val157phe (accessed [today's date]).

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