Is CCN6 p.Glu84Lys (c.250G>A) pathogenic?

CCN6 p.Glu84Lys (c.250G>A) is classified Uncertain significance in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.1726); Absent from gnomAD v4.1.

How common is CCN6 p.Glu84Lys (c.250G>A) in the general population?

CCN6 p.Glu84Lys (c.250G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCN6 p.Glu84Lys (c.250G>A)?

AlphaMissense predicts likely benign (score 0.1726) — an in-silico prediction, not a clinical call.

CCN6 p.Glu84Lys

c.250G>A · rs1776510387 · VCV1913840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1726	likely benign
REVEL	0.53	indeterminate
SaProt	LLR -11.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.028 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCN6
Protein: p.Glu84Lys
Coding: c.250G>A
MANE Select: NM_198239
dbSNP: rs1776510387
Type: single nucleotide variant
Location: chr6:112061192 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 84: a UniProt-annotated variant site (in pprd); the igfbp n-terminal domain

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

Similar variants

CCN6 p.Glu84fs Pathogenic ★★ same residue
CCN6 c.49-1G>A Pathogenic/Likely pathogenic ★★ same type
CCN6 c.590-1G>C Likely pathogenic ★★ same type
CCN6 p.Ala197Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
CCN6 p.Cys223Gly Pathogenic ★★ same type
CCN6 p.Cys337Tyr Pathogenic/Likely pathogenic ★★ same type
CCN6 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same type
CCN6 p.Cys78Tyr Pathogenic/Likely pathogenic ★★ 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/ccn6-p-glu84lys (accessed [today's date]).

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