Is C7 p.Pro135del (c.397CCT[2]) pathogenic?

C7 p.Pro135del (c.397CCT[2]) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-17). Very rare (popmax 0.00585%, nfe).

How common is C7 p.Pro135del (c.397CCT[2]) in the general population?

C7 p.Pro135del (c.397CCT[2]) is very rare (popmax 0.00585%, nfe) (gnomAD).

C7 p.Pro135del

c.397CCT[2] · rs763064315 · VCV2190260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.078	GERP -2.6, phastCons 0.056
Overall
CADD	14.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00585% European (non-Finnish) · 69/1,179,428 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.0044% 71/1,612,886 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,093
Remaining individualsnot grpmax-eligible	0.0016%	62,438
African / African-American	0.00134%	74,826

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: C7
Protein: p.Pro135del
Coding: c.397CCT[2]
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs763064315
Type: Microsatellite
Location: chr5:40936454 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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C7 c.2166-1_2166insGCTGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCGGATCACGAGGTCAGGAGATCGAGACCATACTGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAATTCTTTTCAG Pathogenic ★ same type
C7 p.Leu286fs Pathogenic ★ same type
C7 p.Glu615del Uncertain significance ★ same type
C7 p.Ser232del Uncertain significance ★ same type
C7 c.*96TCT[1] Benign ★ same type
C7 p.Val714fs 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/c7-p-pro135del (accessed [today's date]).

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