Is CREG2 p.Arg288Gly (c.862A>G) pathogenic?

CREG2 p.Arg288Gly (c.862A>G) is classified Uncertain significance in CREG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0951); Ultra-rare (popmax 0.0759%, afr).

How common is CREG2 p.Arg288Gly (c.862A>G) in the general population?

CREG2 p.Arg288Gly (c.862A>G) is ultra-rare (popmax 0.0759%, afr) (gnomAD).

What do computational predictors say about CREG2 p.Arg288Gly (c.862A>G)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

CREG2 p.Arg288Gly

c.862A>G · rs139260475 · VCV3077386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0759%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -6.12	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 2.5	phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 33 kb · p 0.76 · regional, not allelic
Overall
CADD	18.98	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 0.0759% African / African-American · 57/75,064 alleles

Filtering AF 0.0601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0544%

Overall 0.00477% 77/1,614,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0759%	1,317
Admixed American	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	8.47e-05%	1,180,020

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: CREG2
Protein: p.Arg288Gly
Coding: c.862A>G
MANE Select: NM_153836
dbSNP: rs139260475
Type: single nucleotide variant
Location: chr2:101350934 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.48

Full CREG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREG2 p.Ala133Val Uncertain significance ★ ⚠ same type
CREG2 p.Ala290Ser Uncertain significance ★ ⚠ same type
CREG2 p.Ala290Val Uncertain significance ★ ⚠ same type
CREG2 p.Ala29Ser Uncertain significance ★ ⚠ same type
CREG2 p.Ala29Thr Uncertain significance ★ ⚠ same type
CREG2 p.Ala30Glu Uncertain significance ★ ⚠ same type
CREG2 p.Ala92Val Uncertain significance ★ ⚠ same type
CREG2 p.Ala99Pro 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/creg2-p-arg288gly (accessed [today's date]).

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