Is CTF1 p.Ala156fs (c.465dup) pathogenic?

CTF1 p.Ala156fs (c.465dup) is classified Uncertain significance in CTF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-11-02). Very rare (popmax 0.00472%, afr); Associated with dilated cardiomyopathy.

What condition is associated with CTF1 p.Ala156fs (c.465dup)?

CTF1 p.Ala156fs (c.465dup) is associated with dilated cardiomyopathy (ClinVar).

How common is CTF1 p.Ala156fs (c.465dup) in the general population?

CTF1 p.Ala156fs (c.465dup) is very rare (popmax 0.00472%, afr) (gnomAD).

CTF1 p.Ala156fs

c.465dup · rs1218236539 · VCV689586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00472%, afr)

Conditions

dilated cardiomyopathy

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 0.88	GERP -1.2, phastCons 0.13
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CGCCGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00472% African / African-American · 3/63,518 alleles

Filtering AF 0.00125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000648%

Overall 0.00104% 13/1,248,392 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00472%	21,173
Admixed American	0.00408%	24,526
East Asian	0.00335%	29,828
South Asian	0.00283%	35,276
European (non-Finnish)	0.000702%	142,387

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.Ala156fs
Coding: c.465dup
MANE Select: NM_001330
dbSNP: rs1218236539
Type: Duplication
Location: chr16:30902392 (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

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTF1 p.Ala156Thr Uncertain significance ★★ ⚠ same residue
CTF1 p.Ala156= Likely benign same residue
CTF1 p.Leu132Arg Uncertain significance ★ ⚠ same condition
CTF1 p.Ala170fs Uncertain significance ★★ same type
CTF1 p.Ala95_Pro99dup Uncertain significance ★ same type
CTF1 p.Gly149_Ala152dup Uncertain significance ★ same type
CTF1 p.Leu97_Pro98insAlaAlaLeu Uncertain significance ★ same type
CTF1 p.Pro154_Pro155insArgAlaGluPro 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-ala156fs (accessed [today's date]).

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