Is CCN1 p.Ser316Cys (c.947C>G) pathogenic?

CCN1 p.Ser316Cys (c.947C>G) is classified Likely benign in CCN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely pathogenic (0.7747); Rare (popmax 0.818%, nfe).

How common is CCN1 p.Ser316Cys (c.947C>G) in the general population?

CCN1 p.Ser316Cys (c.947C>G) is rare (popmax 0.818%, nfe) (gnomAD).

What do computational predictors say about CCN1 p.Ser316Cys (c.947C>G)?

AlphaMissense predicts likely pathogenic (score 0.7747) — an in-silico prediction, not a clinical call.

CCN1 p.Ser316Cys

c.947C>G · rs148330006 · VCV712918

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7747 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.818%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7747	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.063, phastCons 1
Overall
CADD	28.6	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 0.818% European (non-Finnish) · 9,652/1,180,032 alleles

Filtering AF 0.804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.799%

Overall 0.682% 11,011/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.818%	122
Remaining individualsnot grpmax-eligible	0.704%	142
Finnishnot grpmax-eligible	0.398%	251
Admixed American	0.36%	278
South Asian	0.321%	312
Middle Eastern	0.313%	319
African / African-American	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.128%	779

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: CCN1
Protein: p.Ser316Cys
Coding: c.947C>G
MANE Select: NM_001237 · reported on NM_001554
dbSNP: rs148330006
Type: single nucleotide variant
Location: chr1:85582843 (GRCh38)
Structure: AlphaFold pLDDT 73.80 · 115 PDB
Residue 316: an α-helix

Full CCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCN1 p.Ser316Ala Uncertain significance ★ ⚠ same residue
EXOSC9 p.Ala438Val Uncertain significance ★★ ⚠ same type
CCN1 c.277+50G>C Benign ★★ same type
CCN1 c.64-124G>A Benign ★★ same type
CCN1 c.-107C>A Benign ★★ same type
CCN1 p.Tyr300= Benign ★★ same type
CCNA2 c.*828C>G Benign ★★ same type
CCNA2 p.Leu126= Benign ★★ 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/ccn1-p-ser316cys (accessed [today's date]).

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