Is C8B p.Gln119Ter (c.355C>T) pathogenic?

C8B p.Gln119Ter (c.355C>T) is classified Pathogenic in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-15). Very rare (popmax 6.84e-05%).

How common is C8B p.Gln119Ter (c.355C>T) in the general population?

C8B p.Gln119Ter (c.355C>T) is very rare (popmax 6.84e-05%) (gnomAD).

C8B p.Gln119Ter

c.355C>T · rs760669928 · VCV1457268

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 6.84e-05%)

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	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	Δ0.38	donor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Overall
CADD	43.0	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 6.84e-05%

Overall 6.84e-05% 1/1,461,824 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: C8B
Protein: p.Gln119Ter
Coding: c.355C>T
MANE Select: NM_000066
dbSNP: rs760669928
Type: single nucleotide variant
Location: chr1:56956805 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 119: a UniProt-annotated variant site (in c8d2)

Full C8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8B p.Arg284Ter Pathogenic ★★ same type
C8B p.Arg428Ter Pathogenic ★★ same type
C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Trp9Ter Pathogenic ★★ same type
C8B p.Ala21Thr Uncertain significance ★★ ⚠ same type
C8B p.Ala446Val Uncertain significance ★★ ⚠ same type
C8B p.Ala461Ser 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/c8b-p-gln119ter (accessed [today's date]).

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