Is ACD p.Ser352= (c.1056C>T) pathogenic?

ACD p.Ser352= (c.1056C>T) is classified Likely benign in ACD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0335%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Ser352= (c.1056C>T)?

ACD p.Ser352= (c.1056C>T) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Ser352= (c.1056C>T) in the general population?

ACD p.Ser352= (c.1056C>T) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

ACD p.Ser352=

c.1056C>T · rs200227116 · VCV1769742

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, 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 · G>C here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.83	GERP -2.8, phastCons 0.043
Overall
CADD	1.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% East Asian · 15/44,784 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.001% 16/1,600,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0335%	2,986
Remaining individualsnot grpmax-eligible	0.00162%	61,904

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.Ser352=
Coding: c.1056C>T
MANE Select: NM_001082486
dbSNP: rs200227116
Type: single nucleotide variant
Location: chr16:67658136 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 352: the 'disordered' region

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 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-p-ser352 (accessed [today's date]).

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