Is C7 p.Ser212fs (c.633_643del) pathogenic?

C7 p.Ser212fs (c.633643del) is classified Pathogenic/Likely pathogenic in C7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-07-28). Very rare (popmax 0.00975%, nfe); Associated with C7-related disorders.

What condition is associated with C7 p.Ser212fs (c.633_643del)?

C7 p.Ser212fs (c.633_643del) is associated with C7-related disorders, complement component 7 deficiency (ClinVar).

How common is C7 p.Ser212fs (c.633_643del) in the general population?

C7 p.Ser212fs (c.633_643del) is very rare (popmax 0.00975%, nfe) (gnomAD).

C7 p.Ser212fs

c.633_643del · rs770367814 · VCV871489

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00975%, nfe)

Conditions

C7-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -4.9
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00975% European (non-Finnish) · 113/1,158,882 alleles

Filtering AF 0.00824% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00774%

Overall 0.00779% 123/1,579,356 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00978%	10,222
European (non-Finnish)grpmax	0.00975%	10,256
Finnishnot grpmax-eligible	0.00628%	15,918

Remaining individuals 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: C7
Protein: p.Ser212fs
Coding: c.633_643del
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs770367814
Type: Deletion
Location: chr5:40945261 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

C7-related disorders

Also linked: complement component 7 deficiency

Similar variants

C7 c.2350+1del Likely pathogenic ★★ same condition
C7 p.Asn136fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Cys85fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Lys438fs Pathogenic ★ same condition
C7 p.Ser212Leu Uncertain significance ★ ⚠ same residue
C7 p.Ser212= Likely benign ★ same residue
C7 p.Asp106fs Pathogenic same condition
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ 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/c7-p-ser212fs (accessed [today's date]).

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