Is PC p.Gln348fs (c.1043del) pathogenic?

PC p.Gln348fs (c.1043del) is classified Likely pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-14). Very rare (popmax 0.00135%, afr).

How common is PC p.Gln348fs (c.1043del) in the general population?

PC p.Gln348fs (c.1043del) is very rare (popmax 0.00135%, afr) (gnomAD).

PC p.Gln348fs

c.1043del · rs1064796030 · VCV422831

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Overall
CADD	34.0	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 0.00135% African / African-American · 1/74,086 alleles

Overall 6.21e-05% 1/1,611,404 alleles · very rare exomes 0/1,460,916 · genomes 1/150,488 · joint denominator

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: PC
Protein: p.Gln348fs
Coding: c.1043del
MANE Select: NM_001040716
dbSNP: rs1064796030
Type: Deletion
Location: chr11:66866329 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB
Residue 348: the biotin carboxylation domain; the atp-grasp domain; an α-helix

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

Similar variants

PC p.Gln348Ter Pathogenic ★ same residue
PC c.2473+2_2473+5del Pathogenic/Likely pathogenic ★★ same type
PC p.Arg571fs Pathogenic/Likely pathogenic ★★ same type
PC p.Cys752fs Pathogenic/Likely pathogenic ★★ same type
PC p.Gly303fs Pathogenic/Likely pathogenic ★★ same type
PC p.Leu1030fs Pathogenic/Likely pathogenic ★★ same type
PC p.Leu1137fs Pathogenic/Likely pathogenic ★★ same type
PC p.Lys1130fs 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/pc-p-gln348fs (accessed [today's date]).

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