Is ACD c.413+3A>G pathogenic?

ACD c.413+3A>G is classified Benign/Likely benign in ACD (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Common (popmax 39.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD c.413+3A>G?

ACD c.413+3A>G is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

ACD c.413+3A>G

Q: How common is ACD c.413+3A>G in the general population?

ACD c.413+3A>G is common (popmax 39.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs8058187 · VCV1167322

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 39.6%, 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 +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP -0.32, phastCons 1
Non-coding constraint	Z 3.98	1 kb window · o/e 0.76 · regional · uncalibrated
Overall
CADD	18.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.6% African / African-American · 29,648/74,938 alleles

Filtering AF 39.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 39%

Overall 2.73% 43,977/1,612,960 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	39.6%	3
South Asian	9.57%	10
Remaining individualsnot grpmax-eligible	3.39%	30
Admixed American	2.93%	34
Middle Eastern	2.89%	35
Ashkenazi Jewishnot grpmax-eligible	0.166%	604
East Asian	0.143%	701
European (non-Finnish)	0.122%	817
Finnishnot grpmax-eligible	0.0126%	7,959

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.413+3A>G
MANE Select: NM_001082486
dbSNP: rs8058187
Type: single nucleotide variant
Location: chr16:67659534 (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-413-plus-3a-g (accessed [today's date]).

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