Is CIBAR2 p.Phe25Tyr (c.74T>A) pathogenic?

CIBAR2 p.Phe25Tyr (c.74T>A) is classified Uncertain significance in CIBAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.26); Very rare (popmax 0.00167%, amr).

How common is CIBAR2 p.Phe25Tyr (c.74T>A) in the general population?

CIBAR2 p.Phe25Tyr (c.74T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CIBAR2 p.Phe25Tyr (c.74T>A)?

AlphaMissense predicts likely benign (score 0.26) — an in-silico prediction, not a clinical call.

CIBAR2 p.Phe25Tyr

c.74T>A · rs199902827 · VCV3144955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.26 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.26	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 13 kb · p 6.2e-07 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00167% Admixed American · 1/59,890 alleles

Overall 6.85e-05% 1/1,460,494 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.Phe25Tyr
Coding: c.74T>A
MANE Select: NM_198491
dbSNP: rs199902827
Type: single nucleotide variant
Location: chr16:85110407 (GRCh38)
Gene constraint: LOEUF 1.39 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 25: 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-phe25tyr (accessed [today's date]).

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