Is ABHD12 p.His320= (c.960C>T) pathogenic?

ABHD12 p.His320= (c.960C>T) is classified Conflicting classifications of pathogenicity in ABHD12 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-19). Rare (popmax 0.28%, mid); Associated with PHARC syndrome.

What condition is associated with ABHD12 p.His320= (c.960C>T)?

ABHD12 p.His320= (c.960C>T) is associated with PHARC syndrome (ClinVar).

How common is ABHD12 p.His320= (c.960C>T) in the general population?

ABHD12 p.His320= (c.960C>T) is rare (popmax 0.28%, mid) (gnomAD).

ABHD12 p.His320=

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.960C>T · rs146195280 · VCV895670

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.28%, mid)

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 1.9	GERP -2, phastCons 1
Overall
CADD	7.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.28% Middle Eastern · 17/6,062 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.05% 807/1,613,768 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.28%	357
South Asian	0.0834%	1,198
Remaining individualsnot grpmax-eligible	0.0592%	1,689
European (non-Finnish)	0.0547%	1,829
Admixed American	0.0283%	3,530
Finnishnot grpmax-eligible	0.0189%	5,304
African / African-American	0.004%	25,023

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.His320=
Coding: c.960C>T
MANE Select: NM_001042472
dbSNP: rs146195280
Type: single nucleotide variant
Location: chr20:25303619 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 320: 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.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
ABHD12 p.Arg292Gln 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-his320 (accessed [today's date]).

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