Is CIB3 p.Pro69Ser (c.205C>T) pathogenic?

CIB3 p.Pro69Ser (c.205C>T) is classified Uncertain significance in CIB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely pathogenic (0.9803); Absent from gnomAD v4.1.

How common is CIB3 p.Pro69Ser (c.205C>T) in the general population?

CIB3 p.Pro69Ser (c.205C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIB3 p.Pro69Ser (c.205C>T)?

AlphaMissense predicts likely pathogenic (score 0.9803) — an in-silico prediction, not a clinical call.

CIB3 p.Pro69Ser

c.205C>T · rs2512801151 · VCV2526526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9803	likely pathogenic · top 6% in CIB3
REVEL	0.614	indeterminate
SaProt	LLR -12.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 12 kb · p 0.5 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIB3
Protein: p.Pro69Ser
Coding: c.205C>T
MANE Select: NM_054113
dbSNP: rs2512801151
Type: single nucleotide variant
Location: chr19:16168278 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.17 · 3 PDB
Residue 69: the ef-hand 1 domain

Full CIB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB3 p.Ala102Pro Uncertain significance ★ ⚠ same type
CIB3 p.Ala125Val Uncertain significance ★ ⚠ same type
CIB3 p.Ala142Val Uncertain significance ★ ⚠ same type
CIB3 p.Ala38Thr Uncertain significance ★ ⚠ same type
CIB3 p.Arg104Cys Uncertain significance ★ ⚠ same type
CIB3 p.Arg137Gln Uncertain significance ★ ⚠ same type
CIB3 p.Arg137Trp Uncertain significance ★ ⚠ same type
CIB3 p.Arg163Gln 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/cib3-p-pro69ser (accessed [today's date]).

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