Is CCN6 p.Asp28Gly (c.83A>G) pathogenic?

CCN6 p.Asp28Gly (c.83A>G) is classified Uncertain significance in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.063); Very rare (popmax 0.00127%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CCN6 p.Asp28Gly (c.83A>G)?

CCN6 p.Asp28Gly (c.83A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CCN6 p.Asp28Gly (c.83A>G) in the general population?

CCN6 p.Asp28Gly (c.83A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about CCN6 p.Asp28Gly (c.83A>G)?

AlphaMissense predicts likely benign (score 0.063) — an in-silico prediction, not a clinical call.

CCN6 p.Asp28Gly

c.83A>G · VCV4607522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.063	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.30	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 0.42	GERP 1.5, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.028 · regional, not allelic
Overall
CADD	1.136	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 0.00127% European (non-Finnish) · 15/1,180,036 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,054 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: CCN6
Protein: p.Asp28Gly
Coding: c.83A>G
MANE Select: NM_198239
Type: single nucleotide variant
Location: chr6:112061025 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30

Full CCN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCN6 p.Asp28= Likely benign ★ same residue
CCN6 p.Cys337Tyr Pathogenic/Likely pathogenic ★★ same condition
CCN6 p.Ala15Thr Uncertain significance ★★ ⚠ same condition
CCN6 p.Asp253Asn Uncertain significance ★★ ⚠ same condition
CCN6 p.Gln133Glu Uncertain significance ★★ ⚠ same condition
CCN6 p.Gln289His Uncertain significance ★★ ⚠ same condition
CCN6 p.Glu123Lys Uncertain significance ★★ ⚠ same condition
CCN6 p.Lys173Glu Uncertain significance ★★ ⚠ same condition

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/ccn6-p-asp28gly (accessed [today's date]).

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