Is ACER3 p.Thr15= (c.45C>G) pathogenic?

ACER3 p.Thr15= (c.45C>G) is classified Likely benign in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). Very rare (popmax 0.00157%, nfe).

How common is ACER3 p.Thr15= (c.45C>G) in the general population?

ACER3 p.Thr15= (c.45C>G) is very rare (popmax 0.00157%, nfe) (gnomAD).

ACER3 p.Thr15=

c.45C>G · rs138662843 · VCV1644944

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

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 0.8	GERP -0.69, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00157% European (non-Finnish) · 18/1,146,240 alleles

Filtering AF 0.000981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00081%

Overall 0.00116% 18/1,547,578 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: ACER3
Protein: p.Thr15=
Coding: c.45C>G
MANE Select: NM_018367
dbSNP: rs138662843
Type: single nucleotide variant
Location: chr11:76861021 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB

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

Similar variants

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
ACER3 c.320+14A>C 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-thr15 (accessed [today's date]).

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