Is CALB1 p.Asp24Asn (c.70G>A) pathogenic?

CALB1 p.Asp24Asn (c.70G>A) is classified Uncertain significance in CALB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9583); Very rare (popmax 0.00401%, afr).

How common is CALB1 p.Asp24Asn (c.70G>A) in the general population?

CALB1 p.Asp24Asn (c.70G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CALB1 p.Asp24Asn (c.70G>A)?

AlphaMissense predicts likely pathogenic (score 0.9583) — an in-silico prediction, not a clinical call.

CALB1 p.Asp24Asn

c.70G>A · VCV4647726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9583	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 23 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	28.3	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 0.00401% African / African-American · 3/74,860 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,452 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,953
European (non-Finnish)	0.00017%	589,779

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: CALB1
Protein: p.Asp24Asn
Coding: c.70G>A
MANE Select: NM_004929
Type: single nucleotide variant
Location: chr8:90082628 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 82.70 · 1 PDB
Residue 24: the ef-hand 1 domain; a binding site

Full CALB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALB1 p.Asp24His Uncertain significance ★ ⚠ same residue
CALB1 p.Asp201= Benign ★★ same type
CALB1 p.Ala13Pro Uncertain significance ★ ⚠ same type
CALB1 p.Ala46Glu Uncertain significance ★ ⚠ same type
CALB1 p.Asn125Lys Uncertain significance ★ ⚠ same type
CALB1 p.Asn38Ser Uncertain significance ★ ⚠ same type
CALB1 p.Cys257Arg Uncertain significance ★ ⚠ same type
CALB1 p.Glu86Asp 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/calb1-p-asp24asn (accessed [today's date]).

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