Is C7 p.Asn136fs (c.405del) pathogenic?

C7 p.Asn136fs (c.405del) is classified Pathogenic/Likely pathogenic in C7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-30). Rare (popmax 0.316%, afr); Associated with C7-related disorder.

What condition is associated with C7 p.Asn136fs (c.405del)?

C7 p.Asn136fs (c.405del) is associated with C7-related disorder, complement component 7 deficiency (ClinVar).

How common is C7 p.Asn136fs (c.405del) in the general population?

C7 p.Asn136fs (c.405del) is rare (popmax 0.316%, afr) (gnomAD).

C7 p.Asn136fs

c.405del · rs139491301 · VCV432759

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.316%, afr)

Conditions

C7-related disorder

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 4.9	GERP 2.3, phastCons 1
Overall
CADD	21.7	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 0.316% African / African-American · 237/75,020 alleles

Filtering AF 0.283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0153% 247/1,613,212 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.316%	317
Admixed American	0.00835%	11,982
Remaining individualsnot grpmax-eligible	0.0064%	15,616
South Asian	0.0011%	90,982

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.Asn136fs
Coding: c.405del
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs139491301
Type: Deletion
Location: chr5:40936462 (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 disorder

Also linked: complement component 7 deficiency

Similar variants

C7 c.2350+1del Likely pathogenic ★★ same condition
C7 p.Cys85fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Ser212fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Lys438fs Pathogenic ★ same condition
C7 p.Asn136His Uncertain significance ★ ⚠ same residue
C7 p.Asp106fs Pathogenic same condition
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
C7 c.63-1G>A 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-asn136fs (accessed [today's date]).

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