Is ACD p.Pro455fs (c.1364_1367del) pathogenic?

ACD p.Pro455fs (c.13641367del) is classified Uncertain significance in ACD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Pro455fs (c.1364_1367del)?

ACD p.Pro455fs (c.1364_1367del) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Pro455fs (c.1364_1367del) in the general population?

ACD p.Pro455fs (c.1364_1367del) is very rare (popmax 0.00333%, amr) (gnomAD).

ACD p.Pro455fs

c.1364_1367del · rs772312742 · VCV941603

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

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 (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.28	GERP -3.2, phastCons 0.97

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000479% 7/1,461,830 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,007
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000339%	295,002

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: ACD
Protein: p.Pro455fs
Coding: c.1364_1367del
MANE Select: NM_001082486
dbSNP: rs772312742
Type: Deletion
Location: chr16:67657616 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal dominant 6

Similar variants

ACD p.Pro455Ser Uncertain significance ★ ⚠ same residue
ACD p.Pro203fs Uncertain significance ★★ same condition
ACD p.Pro273_Ser276del Uncertain significance ★★ same condition
ACD p.Arg6fs Likely pathogenic ★ same condition
ACD p.Lys84del Pathogenic ★ same condition
ACD p.Thr51fs Likely pathogenic ★ same condition
ACD c.742+4del Uncertain significance ★ same condition
ACD p.Arg393fs Uncertain significance ★ same condition

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/acd-p-pro455fs (accessed [today's date]).

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