Is ACD p.Ala42= (c.126G>A) pathogenic?

ACD p.Ala42= (c.126G>A) is classified Likely benign in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-24). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Ala42= (c.126G>A)?

ACD p.Ala42= (c.126G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Ala42= (c.126G>A) in the general population?

ACD p.Ala42= (c.126G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

ACD p.Ala42=

c.126G>A · rs1309553451 · VCV2586823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

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 1.1	GERP -1.9, phastCons 0.99
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,874 alleles

Overall 6.21e-05% 1/1,609,404 alleles · very rare exomes 1/1,457,058 · genomes 0/152,346 · joint denominator

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.Ala42=
Coding: c.126G>A
MANE Select: NM_001082486
dbSNP: rs1309553451
Type: single nucleotide variant
Location: chr16:67660353 (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.Ala42Pro Uncertain significance ★ same residue
ACD p.Val42= Likely benign ★ same residue
ACD p.Val42Ile Uncertain significance ★★ ⚠ 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
ACD c.-35C>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-ala42 (accessed [today's date]).

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