Is ACD p.Arg46Ser (c.136C>A) pathogenic?

ACD p.Arg46Ser (c.136C>A) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACD p.Arg46Ser (c.136C>A)?

ACD p.Arg46Ser (c.136C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Arg46Ser (c.136C>A) in the general population?

ACD p.Arg46Ser (c.136C>A) is absent from gnomAD v4.1 (gnomAD).

ACD p.Arg46Ser

c.136C>A · rs751398085 · VCV2624827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,108)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.32	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.72	GERP -2.8
Overall
CADD	0.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,108). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACD
Protein: p.Arg46Ser
Coding: c.136C>A
MANE Select: NM_001082486
dbSNP: rs751398085
Type: single nucleotide variant
Location: chr16:67660343 (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

Similar variants

ACD p.Ser46Phe Uncertain significance ★★ ⚠ same residue
ACD p.Arg46His Uncertain significance ★ same residue
ACD p.Arg46Leu Uncertain significance ★ same residue
ACD p.Ser46Thr Uncertain significance ★ ⚠ same residue
ACD p.Ser46= Likely benign ★ same residue
ACD c.-20C>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-arg46ser (accessed [today's date]).

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