Is CGB7 p.Cys54Phe (c.161G>T) pathogenic?

CGB7 p.Cys54Phe (c.161G>T) is classified Uncertain significance in CGB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: likely pathogenic (0.9882); Absent from gnomAD v4.1.

How common is CGB7 p.Cys54Phe (c.161G>T) in the general population?

CGB7 p.Cys54Phe (c.161G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CGB7 p.Cys54Phe (c.161G>T)?

AlphaMissense predicts likely pathogenic (score 0.9882) — an in-silico prediction, not a clinical call.

CGB7 p.Cys54Phe

c.161G>T · rs2513835248 · VCV2266670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9882 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,024)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9882	likely pathogenic · top 2% in CGB7
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -13.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 788 bp · p 0.00043 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,589,024). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CGB7
Protein: p.Cys54Phe
Coding: c.161G>T
MANE Select: NM_001385261
dbSNP: rs2513835248
Type: single nucleotide variant
Location: chr19:49054863 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 54: a disulfide bond

Full CGB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CGB7 p.Ala103Thr Uncertain significance ★ ⚠ same type
CGB7 p.Arg115His Uncertain significance ★ ⚠ same type
CGB7 p.Arg30His Uncertain significance ★ ⚠ same type
CGB7 p.Arg30Pro Uncertain significance ★ ⚠ same type
CGB7 p.Arg63Cys Uncertain significance ★ ⚠ same type
CGB7 p.Arg80Gly Uncertain significance ★ ⚠ same type
CGB7 p.Arg80His Uncertain significance ★ ⚠ same type
CGB7 p.Arg83Cys 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/cgb7-p-cys54phe (accessed [today's date]).

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