Is CIB1 p.Arg72Gln (c.215G>A) pathogenic?

CIB1 p.Arg72Gln (c.215G>A) is classified Uncertain significance in CIB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-15). AlphaMissense: ambiguous (0.3938); Very rare (popmax 0.005%, amr).

How common is CIB1 p.Arg72Gln (c.215G>A) in the general population?

CIB1 p.Arg72Gln (c.215G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CIB1 p.Arg72Gln (c.215G>A)?

AlphaMissense predicts ambiguous (score 0.3938) — an in-silico prediction, not a clinical call.

CIB1 p.Arg72Gln

c.215G>A · rs775605318 · VCV1375453

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3938	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -9.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,398 bp · p 0.67 · regional, not allelic
Overall
CADD	27.9	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 0.005% Admixed American · 3/59,986 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0011%	91,076
European (non-Finnish)	8.47e-05%	1,179,984

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.Arg72Gln
Coding: c.215G>A
MANE Select: NM_006384
dbSNP: rs775605318
Type: single nucleotide variant
Location: chr15:90231488 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 72: a UniProt-annotated variant site (in ev3; absence of cib1 protein in homozygous patient cells); an α-helix

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

Similar variants

CIB1 p.Arg72Ter Pathogenic ★ 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
CIB1 p.Asn155Asp Uncertain significance ★★ ⚠ same type
CIB1 p.Asn169Ser 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-arg72gln (accessed [today's date]).

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