Is C7 p.Trp205Ter (c.614G>A) pathogenic?

C7 p.Trp205Ter (c.614G>A) is classified Pathogenic/Likely pathogenic in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00728%, sas); Associated with complement component 7 deficiency.

What condition is associated with C7 p.Trp205Ter (c.614G>A)?

C7 p.Trp205Ter (c.614G>A) is associated with complement component 7 deficiency (ClinVar).

How common is C7 p.Trp205Ter (c.614G>A) in the general population?

C7 p.Trp205Ter (c.614G>A) is very rare (popmax 0.00728%, sas) (gnomAD).

C7 p.Trp205Ter

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.614G>A · rs769984570 · VCV1723217

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00728%, sas)

Conditions

complement component 7 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Pangolin	Δ0.27	loss · gain 0.12 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Overall
CADD	40.0	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 0.00728% South Asian · 6/82,426 alleles

Filtering AF 0.00311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.000644% 10/1,552,724 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00728%	13,738
Admixed American	0.00198%	50,546
European (non-Finnish)	0.000262%	381,541

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.Trp205Ter
Coding: c.614G>A
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs769984570
Type: single nucleotide variant
Location: chr5:40945244 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

complement component 7 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
C7 c.63-1G>A Pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
C7 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg402Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg618Trp Uncertain significance ★★ ⚠ same condition
C7 p.Asn202Ser Uncertain significance ★★ ⚠ same condition
C7 p.Gln415Arg Uncertain significance ★★ ⚠ 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-trp205ter (accessed [today's date]).

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