Is CTF1 p.Pro116fs (c.345_346dup) pathogenic?

CTF1 p.Pro116fs (c.345346dup) is classified Uncertain significance in CTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-14). Very rare (popmax 0.00424%, sas).

How common is CTF1 p.Pro116fs (c.345_346dup) in the general population?

CTF1 p.Pro116fs (c.345_346dup) is very rare (popmax 0.00424%, sas) (gnomAD).

CTF1 p.Pro116fs

c.345_346dup · rs1167643962 · VCV478118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00424%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% South Asian · 1/23,558 alleles

Overall 0.000223% 2/896,442 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00424%	23,558
European (non-Finnish)	0.000115%	870,049

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: CTF1
Protein: p.Pro116fs
Coding: c.345_346dup
MANE Select: NM_001330
dbSNP: rs1167643962
Type: Microsatellite
Location: chr16:30902270 (GRCh38)
Gene constraint: LOEUF 1.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94

Full CTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTF1 p.Pro116Arg Uncertain significance ★★ ⚠ same residue
CTF1 p.Pro116Leu Uncertain significance ★★ ⚠ same residue
CTF1 p.Pro116_Ala125del Uncertain significance ★ same residue
CTF1 p.Pro116Ala Uncertain significance ★ ⚠ same residue
CTF1 p.Pro116Thr Uncertain significance ★ same residue
CTF1 p.Leu118fs Uncertain significance ★ same type
CTF1 p.Leu196dup 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/ctf1-p-pro116fs (accessed [today's date]).

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