Is CCN6 p.Cys238Ter (c.714T>A) pathogenic?

CCN6 p.Cys238Ter (c.714T>A) is classified Pathogenic in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Very rare (popmax 0.00133%, afr).

How common is CCN6 p.Cys238Ter (c.714T>A) in the general population?

CCN6 p.Cys238Ter (c.714T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

CCN6 p.Cys238Ter

c.714T>A · rs1776761448 · VCV954611

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -2.4, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,968 alleles

Overall 6.84e-05% 1/1,461,066 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.Cys238Ter
Coding: c.714T>A
MANE Select: NM_198239
dbSNP: rs1776761448
Type: single nucleotide variant
Location: chr6:112068329 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 238: a UniProt-annotated variant site (in pprd); the tsp type-1 domain

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

Similar variants

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
CCN6 p.Met1Val 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-cys238ter (accessed [today's date]).

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