Is C7 p.Arg372Ter (c.1114C>T) pathogenic?

C7 p.Arg372Ter (c.1114C>T) is classified Pathogenic in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). Very rare (popmax 0.00134%, afr).

How common is C7 p.Arg372Ter (c.1114C>T) in the general population?

C7 p.Arg372Ter (c.1114C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

C7 p.Arg372Ter

c.1114C>T · VCV4772136

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 0.00134%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -2.4
Overall
CADD	25.1	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 0.00134% African / African-American · 1/74,642 alleles

Overall 0.000124% 2/1,609,004 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,306
African / African-Americangrpmax	0.00134%	74,642

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.Arg372Ter
Coding: c.1114C>T
MANE Select: NM_001565 · reported on NM_000587
Type: single nucleotide variant
Location: chr5:40955407 (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 p.Arg372Gln Uncertain significance ★★ ⚠ same residue
C7 p.Arg372= Likely benign ★ same residue
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

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-arg372ter (accessed [today's date]).

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