Is ACD p.Pro270del (c.805CCT[1]) pathogenic?

ACD p.Pro270del (c.805CCT[1]) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). Ultra-rare (popmax 0.0135%, afr); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Pro270del (c.805CCT[1])?

ACD p.Pro270del (c.805CCT[1]) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Pro270del (c.805CCT[1]) in the general population?

ACD p.Pro270del (c.805CCT[1]) is ultra-rare (popmax 0.0135%, afr) (gnomAD).

ACD p.Pro270del

c.805CCT[1] · rs762307705 · VCV2883930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, afr)

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP 0.34, phastCons 0.008
Overall
CADD	8.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% African / African-American · 10/73,900 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00102% 16/1,569,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0135%	7,390
South Asian	0.0024%	41,658
Remaining individualsnot grpmax-eligible	0.00165%	60,470
European (non-Finnish)	0.000259%	385,496

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.Pro270del
Coding: c.805CCT[1]
MANE Select: NM_001082486
dbSNP: rs762307705
Type: Microsatellite
Location: chr16:67658574 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 270: the 'disordered' region

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

Disease context

dyskeratosis congenita, autosomal dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACD p.Pro270Leu Uncertain significance ★★ ⚠ same residue
ACD p.Glu83del Pathogenic ★ same condition
ACD c.830-11CTC[2] Uncertain significance ★ same condition
ACD p.Glu21fs Uncertain significance ★ same condition
ACD p.Pro270Ser Uncertain significance ★ ⚠ same residue
ACD p.Pro270Thr Uncertain significance ★ ⚠ same residue
ACD c.337-5_337-3del Likely benign ★ same condition
ACD c.645+2T>C 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-pro270del (accessed [today's date]).

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