Is CREG2 p.Val3Leu (c.7G>T) pathogenic?

CREG2 p.Val3Leu (c.7G>T) is classified Uncertain significance in CREG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1065); Ultra-rare (popmax 0.0432%, eas).

How common is CREG2 p.Val3Leu (c.7G>T) in the general population?

CREG2 p.Val3Leu (c.7G>T) is ultra-rare (popmax 0.0432%, eas) (gnomAD).

What do computational predictors say about CREG2 p.Val3Leu (c.7G>T)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

CREG2 p.Val3Leu

c.7G>T · rs1266439930 · VCV2399685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0432%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.42	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 2.2	GERP 2.4, phastCons 0.22
Regional constraint	o/e 0.97	unconstrained · MANE · 361 bp · p 0.64 · regional, not allelic
Overall
CADD	13.85	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 0.0432% East Asian · 13/30,074 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0202%

Overall 0.00201% 24/1,195,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0432%	2,313
Remaining individualsnot grpmax-eligible	0.00917%	10,900
African / African-American	0.0016%	62,682
European (non-Finnish)	0.000632%	158,171

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.Val3Leu
Coding: c.7G>T
MANE Select: NM_153836
dbSNP: rs1266439930
Type: single nucleotide variant
Location: chr2:101387451 (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-val3leu (accessed [today's date]).

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