Is CIB3 p.Leu41= (c.123C>T) pathogenic?

CIB3 p.Leu41= (c.123C>T) is classified Likely benign in CIB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Rare (popmax 0.514%, nfe).

How common is CIB3 p.Leu41= (c.123C>T) in the general population?

CIB3 p.Leu41= (c.123C>T) is rare (popmax 0.514%, nfe) (gnomAD).

CIB3 p.Leu41=

c.123C>T · rs111791587 · VCV2649507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.514%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.6
Overall
CADD	1.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.514% European (non-Finnish) · 6,063/1,179,410 alleles

Filtering AF 0.503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.499%

Overall 0.453% 7,304/1,612,976 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.2%	84
European (non-Finnish)grpmax	0.514%	195
Remaining individualsnot grpmax-eligible	0.378%	265
Amishnot grpmax-eligible	0.33%	303
Admixed American	0.284%	352
African / African-American	0.0653%	1,531
Ashkenazi Jewishnot grpmax-eligible	0.0474%	2,110
Middle Eastern	0.033%	3,027
East Asian	0.00446%	22,424

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CIB3
Protein: p.Leu41=
Coding: c.123C>T
MANE Select: NM_054113
dbSNP: rs111791587
Type: single nucleotide variant
Location: chr19:16169705 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.17 · 3 PDB
Residue 41: a turn

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-leu41 (accessed [today's date]).

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