Is CSN2 p.Val39Phe (c.115G>T) pathogenic?

CSN2 p.Val39Phe (c.115G>T) is classified Likely benign in CSN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1212); Very rare (popmax 8.55e-05%, nfe).

How common is CSN2 p.Val39Phe (c.115G>T) in the general population?

CSN2 p.Val39Phe (c.115G>T) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about CSN2 p.Val39Phe (c.115G>T)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

CSN2 p.Val39Phe

c.115G>T · rs1723485421 · VCV2484927

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.69	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 -1.8	GERP -3.8
Regional constraint	o/e 1.26	unconstrained · MANE · 4,642 bp · p 2.6e-05 · regional, not allelic
Overall
CADD	4.457	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 8.55e-05% European (non-Finnish) · 1/1,168,932 alleles

Overall 6.92e-05% 1/1,446,046 alleles · very rare

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: CSN2
Protein: p.Val39Phe
Coding: c.115G>T
MANE Select: NM_001891
dbSNP: rs1723485421
Type: single nucleotide variant
Location: chr4:69958938 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.09

Full CSN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSN2 p.Ala162Thr Uncertain significance ★ ⚠ same type
CSN2 p.Ala190Gly Uncertain significance ★ ⚠ same type
CSN2 p.Ala85Pro Uncertain significance ★ ⚠ same type
CSN2 p.Arg189Lys Uncertain significance ★ ⚠ same type
CSN2 p.Asp106Asn Uncertain significance ★ ⚠ same type
CSN2 p.Gln194Arg Uncertain significance ★ ⚠ same type
CSN2 p.Glu20Asp Uncertain significance ★ ⚠ same type
CSN2 p.Gly112Arg 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/csn2-p-val39phe (accessed [today's date]).

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