Is ACER3 p.Pro142= (c.426G>A) pathogenic?

ACER3 p.Pro142= (c.426G>A) is classified Benign in ACER3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 75.4%, nfe) — too common for a highly-penetrant pathogenic allele.

ACER3 p.Pro142=

Q: How common is ACER3 p.Pro142= (c.426G>A) in the general population?

ACER3 p.Pro142= (c.426G>A) is common (popmax 75.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.426G>A · rs3740767 · VCV1164299

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 75.4%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.7	GERP -2.2, phastCons 0.5
Overall
CADD	8.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75.4% European (non-Finnish) · 790,393/1,048,144 alleles

Filtering AF 75.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.2%

Overall 71.1% 1,041,292/1,464,408 alleles · common exomes 950,507/1,312,300 · genomes 90,785/152,108 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	77.1%	1
Amishnot grpmax-eligible	76.3%	1
Ashkenazi Jewishnot grpmax-eligible	76.1%	1
European (non-Finnish)grpmax	75.4%	1
South Asian	69.6%	1
Remaining individualsnot grpmax-eligible	69.1%	1
East Asian	67.5%	1
Middle Eastern	67.4%	1
Admixed American	51.4%	2
African / African-American	24.2%	4

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACER3
Protein: p.Pro142=
Coding: c.426G>A
MANE Select: NM_018367
dbSNP: rs3740767
Type: single nucleotide variant
Location: chr11:76990562 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB
Residue 142: an α-helix

Full ACER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACER3 p.Pro142Ser Uncertain significance ★ same residue
ACER3 p.Ala2Pro Uncertain significance ★★ ⚠ same type
ACER3 p.Ala4Thr Uncertain significance ★★ ⚠ same type
ACER3 p.Arg62Gln Uncertain significance ★★ ⚠ same type
ACER3 p.Gly12Asp Uncertain significance ★★ ⚠ same type
ACER3 p.Ile97Leu Uncertain significance ★★ ⚠ same type
ACER3 p.Val206Ile Uncertain significance ★★ ⚠ same type
ACER3 c.214+19C>G Benign ★★ same type

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/acer3-p-pro142 (accessed [today's date]).

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