Is ABHD12 p.Ser392= (c.1176G>A) pathogenic?

ABHD12 p.Ser392= (c.1176G>A) is classified Benign in ABHD12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-19). Low-frequency (popmax 1.96%, sas); Associated with PHARC syndrome.

What condition is associated with ABHD12 p.Ser392= (c.1176G>A)?

ABHD12 p.Ser392= (c.1176G>A) is associated with PHARC syndrome (ClinVar).

How common is ABHD12 p.Ser392= (c.1176G>A) in the general population?

ABHD12 p.Ser392= (c.1176G>A) is low-frequency (popmax 1.96%, sas) (gnomAD).

ABHD12 p.Ser392=

Q: How is Polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-cataract syndrome inherited?

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

c.1176G>A · rs184232860 · VCV337990

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.96%, sas)

Conditions

PHARC syndrome

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 -5.3	GERP -4
Overall
CADD	5.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.96% South Asian · 1,785/91,074 alleles

Filtering AF 1.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.85%

Overall 0.13% 2,092/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.96%	51
East Asian	0.216%	463
Remaining individualsnot grpmax-eligible	0.141%	710
Middle Eastern	0.0825%	1,212
African / African-American	0.0346%	2,887
European (non-Finnish)	0.00712%	14,047
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Admixed American	0.00666%	15,004
Finnishnot grpmax-eligible	0.00156%	63,996

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.Ser392=
Coding: c.1176G>A
MANE Select: NM_001042472
dbSNP: rs184232860
Type: single nucleotide variant
Location: chr20:25300866 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 392: 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

Disease context

PHARC syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-cataract syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ABHD12 p.Ser392Leu Uncertain significance ★★ ⚠ same residue
ABHD12 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same condition
ABHD12 p.Arg352Ter Pathogenic ★★ same condition
ABHD12 c.867+2C>T Uncertain significance ★★ same condition
ABHD12 p.Ala56Val Uncertain significance ★★ ⚠ same condition
ABHD12 p.Ala9Val Uncertain significance ★★ ⚠ same condition
ABHD12 p.Arg218Gln Uncertain significance ★★ ⚠ same condition
ABHD12 p.Arg279His 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/abhd12-p-ser392 (accessed [today's date]).

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