Is ACER3 p.Leu243= (c.727C>T) pathogenic?

ACER3 p.Leu243= (c.727C>T) is classified Likely benign in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Absent from gnomAD v4.1.

How common is ACER3 p.Leu243= (c.727C>T) in the general population?

ACER3 p.Leu243= (c.727C>T) is absent from gnomAD v4.1 (gnomAD).

ACER3 p.Leu243=

c.727C>T · VCV4765560

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss, 23 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP 1.8, phastCons 1
Overall
CADD	8.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACER3
Protein: p.Leu243=
Coding: c.727C>T
MANE Select: NM_018367
Type: single nucleotide variant
Location: chr11:77019753 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB
Residue 243: an α-helix

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-leu243 (accessed [today's date]).

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