Is CBLIF p.Arg156Cys (c.466C>T) pathogenic?

CBLIF p.Arg156Cys (c.466C>T) is classified Uncertain significance in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1993); Very rare (popmax 0.00223%, eas).

How common is CBLIF p.Arg156Cys (c.466C>T) in the general population?

CBLIF p.Arg156Cys (c.466C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CBLIF p.Arg156Cys (c.466C>T)?

AlphaMissense predicts likely benign (score 0.1993) — an in-silico prediction, not a clinical call.

CBLIF p.Arg156Cys

c.466C>T · VCV3263637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1993	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -12.26	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 1.7	GERP 1.4, phastCons 0.006
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.16 · regional, not allelic
Overall
CADD	22.3	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 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000616% 9/1,461,588 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
South Asian	0.0011%	91,068
European (non-Finnish)	0.000593%	168,575

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: CBLIF
Protein: p.Arg156Cys
Coding: c.466C>T
MANE Select: NM_005142
Type: single nucleotide variant
Location: chr11:59842488 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 156: a disulfide bond; an α-helix

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

Similar variants

CBLIF p.Arg156= Likely benign ★ same residue
CBLIF c.79+1G>A Pathogenic ★★ same type
CBLIF p.Ser46Leu Likely pathogenic ★★ ⚠ same type
CBLIF p.Ala377Thr Uncertain significance ★★ ⚠ same type
CBLIF p.Ala377Val Uncertain significance ★★ ⚠ same type
CBLIF p.Arg104Gln Uncertain significance ★★ ⚠ same type
CBLIF p.Arg352Cys Uncertain significance ★★ ⚠ same type
CBLIF p.Arg352His 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/cblif-p-arg156cys (accessed [today's date]).

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