Is ACD c.1298+20C>A pathogenic?

ACD c.1298+20C>A is classified Benign/Likely benign in ACD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 18.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD c.1298+20C>A?

ACD c.1298+20C>A is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

ACD c.1298+20C>A

Q: How common is ACD c.1298+20C>A in the general population?

ACD c.1298+20C>A is common (popmax 18.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs67114979 · VCV1166998

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 18.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +20	near-intronic (+20 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -3.2, phastCons 0.002
Non-coding constraint	Z 4.46	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	7.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.7% African / African-American · 14,021/74,990 alleles

Filtering AF 18.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 9.98% 161,056/1,613,886 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.7%	5
Admixed American	14.3%	7
Finnishnot grpmax-eligible	14.2%	7
Remaining individualsnot grpmax-eligible	9.7%	10
European (non-Finnish)	9.46%	11
South Asian	8.33%	12
Middle Eastern	7.89%	13
Ashkenazi Jewishnot grpmax-eligible	7.3%	14
Amishnot grpmax-eligible	6.8%	15
East Asian	3.21%	31

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
Coding: c.1298+20C>A
MANE Select: NM_001082486
dbSNP: rs67114979
Type: single nucleotide variant
Location: chr16:67657742 (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

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

Similar variants

ACD c.645+2T>C Uncertain significance ★★ same condition
ACD c.99+5G>A Uncertain significance ★★ same condition
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-24C>T Uncertain significance ★★ same condition
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A Uncertain significance ★★ same condition
ACD c.-29C>T Uncertain significance ★★ same condition
ACD c.-30C>T 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-c-1298-plus-20c-a (accessed [today's date]).

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