Is CIB2 p.Asp150Asn (c.448G>A) pathogenic?

CIB2 p.Asp150Asn (c.448G>A) is classified Benign/Likely benign in CIB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0806); Rare (popmax 0.904%, sas).

How common is CIB2 p.Asp150Asn (c.448G>A) in the general population?

CIB2 p.Asp150Asn (c.448G>A) is rare (popmax 0.904%, sas) (gnomAD).

What do computational predictors say about CIB2 p.Asp150Asn (c.448G>A)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

CIB2 p.Asp150Asn

c.448G>A · rs141932061 · VCV197787

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.904%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.85	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 1.7	GERP 1.7, phastCons 0.91
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	21.4	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 0.904% South Asian · 823/91,090 alleles

Filtering AF 0.852% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.832%

Overall 0.12% 1,937/1,614,212 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.904%	111
African / African-American	0.87%	115
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.139%	718
Admixed American	0.125%	800
European (non-Finnish)	0.0245%	4,083

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: CIB2
Protein: p.Asp150Asn
Coding: c.448G>A
MANE Select: NM_006383
dbSNP: rs141932061
Type: single nucleotide variant
Location: chr15:78105833 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 150: a UniProt-annotated variant site (in dfnb48); a UniProt-annotated variant site (in dfnb48; uncertain significance); the ef-hand 3 domain; an α-helix

Full CIB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
CIB2 p.Arg33Ter Pathogenic ★★ same type
CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CIB2 c.198+3A>G Uncertain significance ★★ same type
CIB2 p.Ala108Thr Uncertain significance ★★ ⚠ same type
CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same type
CIB2 p.Arg134Gln Uncertain significance ★★ ⚠ same type
CIB2 p.Arg134Trp 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/cib2-p-asp150asn (accessed [today's date]).

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