Is CREBZF p.Gly41Arg (c.121G>C) pathogenic?

CREBZF p.Gly41Arg (c.121G>C) is classified Uncertain significance in CREBZF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely benign (0.0871); Ultra-rare (popmax 0.0275%, sas).

How common is CREBZF p.Gly41Arg (c.121G>C) in the general population?

CREBZF p.Gly41Arg (c.121G>C) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

What do computational predictors say about CREBZF p.Gly41Arg (c.121G>C)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

CREBZF p.Gly41Arg

c.121G>C · rs775895845 · VCV2517047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.12, phastCons 0.09
Regional constraint	o/e 1.22	unconstrained · MANE · 701 bp · p 7e-05 · regional, not allelic
Overall
CADD	14.19	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 0.0275% South Asian · 25/90,794 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00187% 30/1,608,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,632
Admixed American	0.00338%	29,554
Remaining individualsnot grpmax-eligible	0.00322%	31,056
African / African-American	0.00134%	74,672

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: CREBZF
Protein: p.Gly41Arg
Coding: c.121G>C
MANE Select: NM_001039618
dbSNP: rs775895845
Type: single nucleotide variant
Location: chr11:85664755 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.32 (gnomAD)
Structure: AlphaFold pLDDT 62.65
Residue 41: the 'disordered' region

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

Similar variants

CREBZF p.Gly41Val Uncertain significance ★ ⚠ same residue
CREBZF p.Ala152Thr Uncertain significance ★ ⚠ same type
CREBZF p.Ala182Thr Uncertain significance ★ ⚠ same type
CREBZF p.Ala269Thr Uncertain significance ★ ⚠ same type
CREBZF p.Ala26Thr Uncertain significance ★ ⚠ same type
CREBZF p.Ala39Val Uncertain significance ★ ⚠ same type
CREBZF p.Ala77Thr Uncertain significance ★ ⚠ same type
CREBZF p.Arg186Pro 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/crebzf-p-gly41arg (accessed [today's date]).

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