Is ACD c.413+1G>C pathogenic?

ACD c.413+1G>C is classified Uncertain significance in ACD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-13). Very rare (popmax 0.000678%, nfe); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD c.413+1G>C?

ACD c.413+1G>C is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD c.413+1G>C in the general population?

ACD c.413+1G>C is very rare (popmax 0.000678%, nfe) (gnomAD).

ACD c.413+1G>C

rs767285943 · VCV2173698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.90	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Non-coding constraint	Z 3.98	1 kb window · o/e 0.76 · regional · uncalibrated
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,424 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000548% 8/1,460,782 alleles · very rare

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+1G>C
MANE Select: NM_001082486
dbSNP: rs767285943
Type: single nucleotide variant
Location: chr16:67659536 (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-1g-c (accessed [today's date]).

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