Is ACD p.His332= (c.996C>T) pathogenic?

ACD p.His332= (c.996C>T) is classified Likely benign in ACD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.016%, afr); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.His332= (c.996C>T)?

ACD p.His332= (c.996C>T) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.His332= (c.996C>T) in the general population?

ACD p.His332= (c.996C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

ACD p.His332=

c.996C>T · rs560864093 · VCV1761460

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -0.26
Overall
CADD	1.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/75,046 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00118% 19/1,612,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,254
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0032%	31,236
Admixed American	0.00167%	59,958
European (non-Finnish)	0.00017%	589,762

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.His332=
Coding: c.996C>T
MANE Select: NM_001082486
dbSNP: rs560864093
Type: single nucleotide variant
Location: chr16:67658196 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 332: the 'disordered' region

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 p.His332_Pro340del Uncertain significance ★ same residue
ACD p.His332Asn Uncertain significance ★ ⚠ same residue
ACD p.His332Gln Uncertain significance ★ ⚠ same residue
ACD p.His332Tyr 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

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-his332 (accessed [today's date]).

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