Is ABHD12 p.Ala9Val (c.26C>T) pathogenic?

ABHD12 p.Ala9Val (c.26C>T) is classified Uncertain significance in ABHD12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0789); Ultra-rare (popmax 0.0299%, sas); Associated with PHARC syndrome.

What condition is associated with ABHD12 p.Ala9Val (c.26C>T)?

ABHD12 p.Ala9Val (c.26C>T) is associated with PHARC syndrome (ClinVar).

How common is ABHD12 p.Ala9Val (c.26C>T) in the general population?

ABHD12 p.Ala9Val (c.26C>T) is ultra-rare (popmax 0.0299%, sas) (gnomAD).

What do computational predictors say about ABHD12 p.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

ABHD12 p.Ala9Val

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.26C>T · rs776381886 · VCV898715

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0299%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PHARC syndrome

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.51, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0299% South Asian · 22/73,684 alleles

Filtering AF 0.0202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.00273% 39/1,429,596 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0299%	3,349
Remaining individualsnot grpmax-eligible	0.00554%	18,051
European (non-Finnish)	0.00128%	78,123

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.Ala9Val
Coding: c.26C>T
MANE Select: NM_001042472
dbSNP: rs776381886
Type: single nucleotide variant
Location: chr20:25390678 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60

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.Ala9Thr Uncertain significance ★ ⚠ same residue
ABHD12 p.Ala9= Likely benign ★ 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.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-ala9val (accessed [today's date]).

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