Is CCN1 p.Val55Phe (c.163G>T) pathogenic?

CCN1 p.Val55Phe (c.163G>T) is classified Uncertain significance in CCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.5805); Absent from gnomAD v4.1.

How common is CCN1 p.Val55Phe (c.163G>T) in the general population?

CCN1 p.Val55Phe (c.163G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCN1 p.Val55Phe (c.163G>T)?

AlphaMissense predicts likely pathogenic (score 0.5805) — an in-silico prediction, not a clinical call.

CCN1 p.Val55Phe

c.163G>T · rs2527920745 · VCV3139769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5805	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -14.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CCN1
Protein: p.Val55Phe
Coding: c.163G>T
MANE Select: NM_001237 · reported on NM_001554
dbSNP: rs2527920745
Type: single nucleotide variant
Location: chr1:85581464 (GRCh38)
Structure: AlphaFold pLDDT 73.80 · 115 PDB
Residue 55: the 'disordered' region; a modified residue (phosphoserine); a β-strand

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

Similar variants

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.Ser316Cys Likely 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-val55phe (accessed [today's date]).

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