Is CGB7 p.Val68Ala (c.203T>C) pathogenic?

CGB7 p.Val68Ala (c.203T>C) is classified Likely benign in CGB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.1103); Ultra-rare (popmax 0.0349%, afr).

How common is CGB7 p.Val68Ala (c.203T>C) in the general population?

CGB7 p.Val68Ala (c.203T>C) is ultra-rare (popmax 0.0349%, afr) (gnomAD).

What do computational predictors say about CGB7 p.Val68Ala (c.203T>C)?

AlphaMissense predicts likely benign (score 0.1103) — an in-silico prediction, not a clinical call.

CGB7 p.Val68Ala

c.203T>C · rs1167500738 · VCV2308382

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1103 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1103	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -3.67	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 -0.25
Regional constraint	o/e 0.29	constrained · MANE · 251 bp · p 1e-15 · regional, not allelic
Overall
CADD	0.264	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 0.0349% African / African-American · 22/62,948 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.00211% 25/1,186,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0349%	2,861
Admixed American	0.00444%	22,502
Remaining individualsnot grpmax-eligible	0.00208%	48,176

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: CGB7
Protein: p.Val68Ala
Coding: c.203T>C
MANE Select: NM_001385261
dbSNP: rs1167500738
Type: single nucleotide variant
Location: chr19:49054586 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 68: 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-val68ala (accessed [today's date]).

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