Is CCN6 p.Ser7Pro (c.19T>C) pathogenic?

CCN6 p.Ser7Pro (c.19T>C) is classified Conflicting classifications of pathogenicity in CCN6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.0597); Ultra-rare (popmax 0.0628%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCN6 p.Ser7Pro (c.19T>C)?

CCN6 p.Ser7Pro (c.19T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CCN6 p.Ser7Pro (c.19T>C) in the general population?

CCN6 p.Ser7Pro (c.19T>C) is ultra-rare (popmax 0.0628%, afr) (gnomAD).

What do computational predictors say about CCN6 p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

CCN6 p.Ser7Pro

c.19T>C · rs34322868 · VCV1680452

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0628%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -7.03	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 -3	GERP -3
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.028 · regional, not allelic
Overall
CADD	7.016	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 0.0628% African / African-American · 47/74,794 alleles

Filtering AF 0.0485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0434%

Overall 0.0039% 63/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0628%	1,591
Middle Eastern	0.0493%	2,028
Admixed American	0.0133%	7,495
Remaining individualsnot grpmax-eligible	0.008%	12,496

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.Ser7Pro
Coding: c.19T>C
MANE Select: NM_198239
dbSNP: rs34322868
Type: single nucleotide variant
Location: chr6:112054376 (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.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
CCN6 p.Lys206Glu 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-ser7pro (accessed [today's date]).

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