Is ACD p.His47Asp (c.139C>G) pathogenic?

ACD p.His47Asp (c.139C>G) is classified Uncertain significance in ACD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1118); Very rare (popmax 6.87e-05%); Associated with Inborn genetic diseases.

What condition is associated with ACD p.His47Asp (c.139C>G)?

ACD p.His47Asp (c.139C>G) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.His47Asp (c.139C>G) in the general population?

ACD p.His47Asp (c.139C>G) is very rare (popmax 6.87e-05%) (gnomAD).

What do computational predictors say about ACD p.His47Asp (c.139C>G)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

ACD p.His47Asp

c.139C>G · rs1057522813 · VCV387524

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -4.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.048	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	5.716	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.87e-05%

Overall 6.87e-05% 1/1,455,452 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.His47Asp
Coding: c.139C>G
MANE Select: NM_001082486
dbSNP: rs1057522813
Type: single nucleotide variant
Location: chr16:67660006 (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.Gly47Arg Uncertain significance ★ same residue
ACD p.His47Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ACD p.His47Pro Uncertain significance ★ ⚠ same residue
ACD p.His47Tyr Uncertain significance ★ ⚠ same residue
ACD p.Gly47= Likely benign ★ 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

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-his47asp (accessed [today's date]).

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