Is CBX7 p.Ile230Val (c.688A>G) pathogenic?

CBX7 p.Ile230Val (c.688A>G) is classified Likely benign in CBX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.0747); Ultra-rare (popmax 0.088%, afr).

How common is CBX7 p.Ile230Val (c.688A>G) in the general population?

CBX7 p.Ile230Val (c.688A>G) is ultra-rare (popmax 0.088%, afr) (gnomAD).

What do computational predictors say about CBX7 p.Ile230Val (c.688A>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

CBX7 p.Ile230Val

c.688A>G · rs143968276 · VCV2407193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.088%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -4.37	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 -0.41	GERP -3.4, phastCons 0.21
Regional constraint	o/e 0.92	unconstrained · MANE · 858 bp · p 0.23 · regional, not allelic
Overall
CADD	13.36	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 0.088% African / African-American · 66/75,012 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.00483% 78/1,613,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.088%	1,137
Admixed American	0.00833%	12,001
Remaining individualsnot grpmax-eligible	0.0048%	20,832
European (non-Finnish)	0.000339%	294,970

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: CBX7
Protein: p.Ile230Val
Coding: c.688A>G
MANE Select: NM_175709
dbSNP: rs143968276
Type: single nucleotide variant
Location: chr22:39133959 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 9 PDB
Residue 230: a β-strand; the 'required for cellular lifespan extension' region

Full CBX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX7 p.Ala179Ser Uncertain significance ★ ⚠ same type
CBX7 p.Ala185Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala202Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Pro Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Val Uncertain significance ★ ⚠ same type
CBX7 p.Arg140Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg159Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg170Gln 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/cbx7-p-ile230val (accessed [today's date]).

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