Is CREBL2 p.Met79Val (c.235A>G) pathogenic?

CREBL2 p.Met79Val (c.235A>G) is classified Uncertain significance in CREBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.2958); Very rare (popmax 0.00669%, eas).

How common is CREBL2 p.Met79Val (c.235A>G) in the general population?

CREBL2 p.Met79Val (c.235A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CREBL2 p.Met79Val (c.235A>G)?

AlphaMissense predicts likely benign (score 0.2958) — an in-silico prediction, not a clinical call.

CREBL2 p.Met79Val

c.235A>G · rs779362952 · VCV2214366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2958	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 1,709 bp · p 0.0003 · regional, not allelic
Overall
CADD	21.3	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 0.00669% East Asian · 3/44,816 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000499% 8/1,604,530 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,939
Admixed American	0.00167%	59,772
African / African-American	0.00134%	74,736
South Asian	0.00112%	89,612
European (non-Finnish)	0.00017%	586,992

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: CREBL2
Protein: p.Met79Val
Coding: c.235A>G
MANE Select: NM_001310
dbSNP: rs779362952
Type: single nucleotide variant
Location: chr12:12637591 (GRCh38)
Gene constraint: LOEUF 0.427 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.59
Residue 79: the bzip domain

Full CREBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREBL2 p.Arg58Ter Likely pathogenic ★ same type
CREBL2 p.Ala64Ser Uncertain significance ★ ⚠ same type
CREBL2 p.Asp114His Uncertain significance ★ ⚠ same type
CREBL2 p.Gln81Lys Uncertain significance ★ ⚠ same type
CREBL2 p.Glu87Asp Uncertain significance ★ ⚠ same type
CREBL2 p.Gly15Ser Uncertain significance ★ ⚠ same type
CREBL2 p.Ser100Cys Uncertain significance ★ ⚠ same type
CREBL2 p.Ser105Asn 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/crebl2-p-met79val (accessed [today's date]).

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