Is ABHD12 p.Phe77Ser (c.230T>C) pathogenic?

ABHD12 p.Phe77Ser (c.230T>C) is classified Uncertain significance in ABHD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.2308); Very rare (popmax 0.00333%, amr).

How common is ABHD12 p.Phe77Ser (c.230T>C) in the general population?

ABHD12 p.Phe77Ser (c.230T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABHD12 p.Phe77Ser (c.230T>C)?

AlphaMissense predicts likely benign (score 0.2308) — an in-silico prediction, not a clinical call.

ABHD12 p.Phe77Ser

c.230T>C · rs2089422737 · VCV2089526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2308 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2308	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -6.94	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.94 · regional, not allelic
Overall
CADD	21.7	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 0.00333% Admixed American · 2/60,030 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,614,192 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,015
Remaining individualsnot grpmax-eligible	0.0032%	31,252
African / African-American	0.00133%	75,042

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.Phe77Ser
Coding: c.230T>C
MANE Select: NM_001042472
dbSNP: rs2089422737
Type: single nucleotide variant
Location: chr20:25339313 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.60
Residue 77: a UniProt-annotated variant site (in pharc)

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

Similar variants

ABHD12 p.Phe77Leu Likely benign ★ 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
ABHD12 c.620-3C>T Uncertain significance ★★ same type
ABHD12 c.867+2C>T Uncertain significance ★★ 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-phe77ser (accessed [today's date]).

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