Is C7 p.Gln150Ter (c.448C>T) pathogenic?

C7 p.Gln150Ter (c.448C>T) is classified Pathogenic in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). Very rare (popmax 0.00017%, nfe).

How common is C7 p.Gln150Ter (c.448C>T) in the general population?

C7 p.Gln150Ter (c.448C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

C7 p.Gln150Ter

c.448C>T · rs1225243005 · VCV2990929

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	Δ0.42	acceptor loss, 19 bp away · masked 0 · deltas
Pangolin	Δ0.41	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.18	GERP 1.6
Overall
CADD	35.0	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 0.00017% European (non-Finnish) · 2/1,178,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,609,416 alleles · very rare

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.Gln150Ter
Coding: c.448C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs1225243005
Type: single nucleotide variant
Location: chr5:40937571 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Similar variants

C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
C7 c.63-1G>A Pathogenic ★★ same type
C7 c.739-2A>G Likely pathogenic ★★ same type
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same type
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Ala359Thr Uncertain significance ★★ ⚠ 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-gln150ter (accessed [today's date]).

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