Is ABHD12 p.Ser378= (c.1134C>T) pathogenic?

ABHD12 p.Ser378= (c.1134C>T) is classified Likely benign in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). Very rare (popmax 8.47e-05%, nfe).

How common is ABHD12 p.Ser378= (c.1134C>T) in the general population?

ABHD12 p.Ser378= (c.1134C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ABHD12 p.Ser378=

c.1134C>T · rs2515746288 · VCV3008842

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 1.5	GERP 1.3, phastCons 1
Overall
CADD	7.447	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 0.000137% 2/1,461,252 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)grpmax	8.47e-05%	1,179,994

Remaining individuals 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: ABHD12
Protein: p.Ser378=
Coding: c.1134C>T
MANE Select: NM_001042472
dbSNP: rs2515746288
Type: single nucleotide variant
Location: chr20:25302242 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 378: a UniProt-annotated variant site (in pharc); a UniProt-annotated variant site (in pharc; uncertain significance); a UniProt-annotated variant site (in pharc; abolished monoacyglycerol lipase activity)

Full ABHD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD12 c.1029+1G>T Likely pathogenic ★★ same type
ABHD12 p.Arg262Ter Pathogenic ★★ same type
ABHD12 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
ABHD12 p.Arg352Ter Pathogenic ★★ same type
ABHD12 p.Arg355Ter Pathogenic ★★ same type
ABHD12 c.620-3C>T Uncertain significance ★★ same type
ABHD12 c.867+2C>T Uncertain significance ★★ same type
ABHD12 p.Ala152Thr Uncertain significance ★★ ⚠ 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/abhd12-p-ser378 (accessed [today's date]).

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