Is CIB1 p.Arg50Trp (c.148C>T) pathogenic?

CIB1 p.Arg50Trp (c.148C>T) is classified Likely benign in CIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1102); Rare (popmax 0.216%, eas).

How common is CIB1 p.Arg50Trp (c.148C>T) in the general population?

CIB1 p.Arg50Trp (c.148C>T) is rare (popmax 0.216%, eas) (gnomAD).

What do computational predictors say about CIB1 p.Arg50Trp (c.148C>T)?

AlphaMissense predicts likely benign (score 0.1102) — an in-silico prediction, not a clinical call.

CIB1 p.Arg50Trp

c.148C>T · rs572714028 · VCV1656120

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1102 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.216%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1102	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,398 bp · p 0.67 · regional, not allelic
Overall
CADD	26.1	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 0.216% East Asian · 97/44,822 alleles

Filtering AF 0.182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.00874% 141/1,612,848 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.216%	462
Remaining individualsnot grpmax-eligible	0.0144%	6,940
South Asian	0.0143%	6,992
Admixed American	0.00334%	29,972
European (non-Finnish)	0.00161%	62,057
African / African-American	0.00133%	75,050

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: CIB1
Protein: p.Arg50Trp
Coding: c.148C>T
MANE Select: NM_006384
dbSNP: rs572714028
Type: single nucleotide variant
Location: chr15:90232266 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 50: a turn

Full CIB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB1 p.Arg50Gln Uncertain significance ★ ⚠ same residue
CIB1 p.Arg50Gly Uncertain significance ★ ⚠ same residue
CIB1 p.Arg50Leu Likely benign ★ same residue
CIB1 p.Ala184Pro Uncertain significance ★★ ⚠ same type
CIB1 p.Ala66Thr Uncertain significance ★★ ⚠ same type
CIB1 p.Arg113His Uncertain significance ★★ ⚠ same type
CIB1 p.Arg143Gln Uncertain significance ★★ ⚠ same type
CIB1 p.Arg143Trp 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/cib1-p-arg50trp (accessed [today's date]).

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