Is ABHD12 p.Arg65Ter (c.193C>T) pathogenic?

ABHD12 p.Arg65Ter (c.193C>T) is classified Pathogenic in ABHD12 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-01-27). Ultra-rare (popmax 0.0164%, mid); Associated with ABHD12-related disorder.

What condition is associated with ABHD12 p.Arg65Ter (c.193C>T)?

ABHD12 p.Arg65Ter (c.193C>T) is associated with ABHD12-related disorder, inherited retinal dystrophy (ClinVar).

How common is ABHD12 p.Arg65Ter (c.193C>T) in the general population?

ABHD12 p.Arg65Ter (c.193C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ABHD12 p.Arg65Ter

c.193C>T · rs758316679 · VCV438130

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

ABHD12-related disorder

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 2 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.5, 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.0013% 21/1,613,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00879%	11,383
Admixed American	0.005%	19,993
African / African-American	0.00401%	24,961
European (non-Finnish)	0.000508%	196,664

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.Arg65Ter
Coding: c.193C>T
MANE Select: NM_001042472
dbSNP: rs758316679
Type: single nucleotide variant
Location: chr20:25339350 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 65: a UniProt-annotated variant site (in pharc)

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

Disease context

ABHD12-related disorder

Also linked: inherited retinal dystrophy

Similar variants

ABHD12 p.Arg65Gln Uncertain significance ★ ⚠ same residue
ABHD12 p.Arg262Ter Pathogenic ★★ same condition
ABHD12 p.Arg352Ter Pathogenic ★★ same condition
ABHD12 p.Arg355Ter Pathogenic ★★ same condition
ABHD12 p.Ser21Phe Uncertain significance ★★ ⚠ same condition
ABHD12 c.1157+1G>A Likely pathogenic ★ same condition
ABHD12 c.316+1G>A Likely pathogenic ★ same condition
ABHD12 p.Ala252Val Likely pathogenic ★ ⚠ 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-arg65ter (accessed [today's date]).

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