Is ABHD12 p.Arg292Ter (c.874C>T) pathogenic?

ABHD12 p.Arg292Ter (c.874C>T) is classified Pathogenic/Likely pathogenic in ABHD12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-08). Very rare (popmax 0.00769%, sas); Associated with PHARC syndrome.

What condition is associated with ABHD12 p.Arg292Ter (c.874C>T)?

ABHD12 p.Arg292Ter (c.874C>T) is associated with PHARC syndrome (ClinVar).

How common is ABHD12 p.Arg292Ter (c.874C>T) in the general population?

ABHD12 p.Arg292Ter (c.874C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

ABHD12 p.Arg292Ter

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.874C>T · rs776800006 · VCV452247

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

PHARC syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 13
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Pangolin	Δ0.54	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 1.4, 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 0.00769% South Asian · 7/90,982 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000808% 13/1,608,556 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	12,997
Admixed American	0.00167%	59,998
European (non-Finnish)	0.000425%	235,145

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.Arg292Ter
Coding: c.874C>T
MANE Select: NM_001042472
dbSNP: rs776800006
Type: single nucleotide variant
Location: chr20:25306909 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 292: a UniProt-annotated variant site (in pharc); a UniProt-annotated variant site (in pharc; uncertain significance)

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.Arg292Gln Uncertain significance ★★ ⚠ same residue
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
ABHD12 p.Cys323Arg 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-arg292ter (accessed [today's date]).

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