Is CCN4 p.Asn242= (c.726C>T) pathogenic?

CCN4 p.Asn242= (c.726C>T) is classified Likely benign in CCN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-07). Ultra-rare (popmax 0.0331%, mid).

How common is CCN4 p.Asn242= (c.726C>T) in the general population?

CCN4 p.Asn242= (c.726C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

CCN4 p.Asn242=

c.726C>T · rs201767438 · VCV730932

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -3.8
Overall
CADD	1.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,050 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00719% 116/1,614,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.115%	871
Middle Easterngrpmax	0.0331%	3,025
Admixed American	0.0217%	4,617
European (non-Finnish)	0.00483%	20,702
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00446%	22,438
South Asian	0.00329%	30,359
African / African-American	0.00267%	37,517

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCN4
Protein: p.Asn242=
Coding: c.726C>T
MANE Select: NM_003882
dbSNP: rs201767438
Type: single nucleotide variant
Location: chr8:133225505 (GRCh38)
Gene constraint: LOEUF 1.151 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.16
Residue 242: the tsp type-1 domain

Full CCN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCN4 p.Arg97= Benign ★★ same type
CCN4 p.Leu99= Benign ★★ same type
CCN4 p.Thr145Met Likely benign ★★ ⚠ same type
CCN4 p.Ala10Glu Uncertain significance ★ ⚠ same type
CCN4 p.Ala10Thr Uncertain significance ★ ⚠ same type
CCN4 p.Ala17Ser Uncertain significance ★ ⚠ same type
CCN4 p.Ala196Thr Uncertain significance ★ ⚠ same type
CCN4 p.Ala243Ser 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/ccn4-p-asn242 (accessed [today's date]).

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