Is CIBAR2 p.Arg41Leu (c.122G>T) pathogenic?

CIBAR2 p.Arg41Leu (c.122G>T) is classified Uncertain significance in CIBAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.2445); Very rare (popmax 0.00267%, afr).

How common is CIBAR2 p.Arg41Leu (c.122G>T) in the general population?

CIBAR2 p.Arg41Leu (c.122G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CIBAR2 p.Arg41Leu (c.122G>T)?

AlphaMissense predicts likely benign (score 0.2445) — an in-silico prediction, not a clinical call.

CIBAR2 p.Arg41Leu

c.122G>T · rs748006465 · VCV3144935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2445	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -12.77	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 2.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 13 kb · p 6.2e-07 · regional, not allelic
Overall
CADD	22.7	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 0.00267% African / African-American · 2/74,922 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,192 alleles · very rare

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: CIBAR2
Protein: p.Arg41Leu
Coding: c.122G>T
MANE Select: NM_198491
dbSNP: rs748006465
Type: single nucleotide variant
Location: chr16:85110359 (GRCh38)
Gene constraint: LOEUF 1.39 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 41: the 'bar-like' region

Full CIBAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIBAR2 p.Ala102Thr Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala109Gly Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala153Thr Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala19Gly Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala203Thr Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala249Thr Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala261Glu Uncertain significance ★ ⚠ same type
CIBAR2 p.Ala261Ser 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/cibar2-p-arg41leu (accessed [today's date]).

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