Is ACD p.Arg433= (c.1299G>A) pathogenic?

ACD p.Arg433= (c.1299G>A) is classified Conflicting classifications of pathogenicity in ACD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-01). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Arg433= (c.1299G>A)?

ACD p.Arg433= (c.1299G>A) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Arg433= (c.1299G>A) in the general population?

ACD p.Arg433= (c.1299G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

ACD p.Arg433=

c.1299G>A · rs756845439 · VCV1775178

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -0.92, phastCons 1
Overall
CADD	8.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 6.84e-05% 1/1,461,782 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
Protein: p.Arg433=
Coding: c.1299G>A
MANE Select: NM_001082486
dbSNP: rs756845439
Type: single nucleotide variant
Location: chr16:67657684 (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.Arg433Ser Uncertain significance ★ ⚠ same residue
ACD p.Arg433Trp Uncertain significance ★ ⚠ same residue
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

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-arg433 (accessed [today's date]).

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