Is ACD p.Pro63Ala (c.187C>G) pathogenic?

ACD p.Pro63Ala (c.187C>G) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Pro63Ala (c.187C>G)?

ACD p.Pro63Ala (c.187C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Pro63Ala (c.187C>G) in the general population?

ACD p.Pro63Ala (c.187C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ACD p.Pro63Ala

c.187C>G · rs2142976460 · VCV3232656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.4, phastCons 1
Overall
CADD	16.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,562 alleles

Overall 6.85e-05% 1/1,459,350 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.Pro63Ala
Coding: c.187C>G
MANE Select: NM_001082486
dbSNP: rs2142976460
Type: single nucleotide variant
Location: chr16:67660292 (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.Pro63= Likely benign ★ same residue
ACD p.Gly63Ala Uncertain significance ★ ⚠ same residue
ACD p.Gly63Arg Uncertain significance ★ ⚠ same residue
ACD p.Gly63= 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
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-pro63ala (accessed [today's date]).

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