Is ABHD12 p.Ser23Phe (c.68C>T) pathogenic?

ABHD12 p.Ser23Phe (c.68C>T) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-30). AlphaMissense: likely benign (0.1332); Very rare (popmax 0.00131%, sas).

How common is ABHD12 p.Ser23Phe (c.68C>T) in the general population?

ABHD12 p.Ser23Phe (c.68C>T) is very rare (popmax 0.00131%, sas) (gnomAD).

What do computational predictors say about ABHD12 p.Ser23Phe (c.68C>T)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

ABHD12 p.Ser23Phe

c.68C>T · VCV4944676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00131%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00131% South Asian · 1/76,560 alleles

Overall 0.000154% 2/1,301,364 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00131%	76,560
European (non-Finnish)	9.03e-05%	1,107,584

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.Ser23Phe
Coding: c.68C>T
MANE Select: NM_001042472
Type: single nucleotide variant
Location: chr20:25390636 (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

Similar variants

ABHD12 p.Ser23= Likely benign ★★ same residue
ABHD12 p.Ser23Cys Uncertain significance ★ ⚠ same residue
ABHD12 p.Ser23del Uncertain significance ★★ same residue
ABHD12 c.1029+1G>T Likely pathogenic ★★ same type
ABHD12 p.Arg262Ter Pathogenic ★★ same type
ABHD12 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
ABHD12 p.Arg352Ter Pathogenic ★★ same type
ABHD12 p.Arg355Ter Pathogenic ★★ same type

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-ser23phe (accessed [today's date]).

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