Is CIRBP p.Arg101Trp (c.301C>T) pathogenic?

CIRBP p.Arg101Trp (c.301C>T) is classified Uncertain significance in CIRBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: ambiguous (0.5602); Very rare (popmax 0.00356%, nfe).

How common is CIRBP p.Arg101Trp (c.301C>T) in the general population?

CIRBP p.Arg101Trp (c.301C>T) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about CIRBP p.Arg101Trp (c.301C>T)?

AlphaMissense predicts ambiguous (score 0.5602) — an in-silico prediction, not a clinical call.

CIRBP p.Arg101Trp

c.301C>T · VCV3833566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5602	ambiguous
REVEL	0.202	benign-leaning
SaProt	LLR -15.33	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.7	GERP 0.12, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 1,236 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	32.0	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 0.00356% European (non-Finnish) · 42/1,179,778 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00273% 44/1,613,250 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,090
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	91,044

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: CIRBP
Protein: p.Arg101Trp
Coding: c.301C>T
MANE Select: NM_001300829
Type: single nucleotide variant
Location: chr19:1271419 (GRCh38)
Gene constraint: LOEUF 0.717 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 61.78 · 3 PDB
Residue 101: the 'disordered' region

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

Similar variants

CIRBP p.Arg105Cys Uncertain significance ★ ⚠ same type
CIRBP p.Arg112Cys Uncertain significance ★ ⚠ same type
CIRBP p.Arg112Leu Uncertain significance ★ same type
CIRBP p.Arg116Lys Uncertain significance ★ ⚠ same type
CIRBP p.Arg127Trp Uncertain significance ★ ⚠ same type
CIRBP p.Arg139Thr Uncertain significance ★ ⚠ same type
CIRBP p.Arg154Trp Uncertain significance ★ ⚠ same type
CIRBP p.Arg91His 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/cirbp-p-arg101trp (accessed [today's date]).

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