Is ACER3 p.Arg203Ter (c.607C>T) pathogenic?

ACER3 p.Arg203Ter (c.607C>T) is classified Pathogenic in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). Very rare (popmax 0.000174%, nfe); Associated with alkaline ceramidase 3 deficiency.

What condition is associated with ACER3 p.Arg203Ter (c.607C>T)?

ACER3 p.Arg203Ter (c.607C>T) is associated with alkaline ceramidase 3 deficiency (ClinVar).

How common is ACER3 p.Arg203Ter (c.607C>T) in the general population?

ACER3 p.Arg203Ter (c.607C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

How is Alkaline ceramidase 3 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACER3 p.Arg203Ter

c.607C>T · rs782709009 · VCV548629

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

alkaline ceramidase 3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.76, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,151,722 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000142% 2/1,413,086 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.Arg203Ter
Coding: c.607C>T
MANE Select: NM_018367
dbSNP: rs782709009
Type: single nucleotide variant
Location: chr11:77016682 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB
Residue 203: an α-helix

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

Disease context

alkaline ceramidase 3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alkaline ceramidase 3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

ACER3 p.Arg203Gln Uncertain significance ★ ⚠ same residue
ACER3 p.Arg159Ter Likely pathogenic ★ same condition
ACER3 p.Gly211Cys Pathogenic ★ same condition
ACER3 p.Ser235Arg Pathogenic ★ ⚠ same condition
ACER3 p.Cys196Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
ACER3 p.Glu33Gly Uncertain significance ★ ⚠ same condition
ACER3 p.Phe80Leu Uncertain significance ★ ⚠ same condition
ACER3 p.Trp78Arg 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/acer3-p-arg203ter (accessed [today's date]).

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