Is ABHD4 p.Pro178Ser (c.532C>T) pathogenic?

ABHD4 p.Pro178Ser (c.532C>T) is classified Uncertain significance in ABHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: ambiguous (0.3928); Very rare (popmax 0.00267%, afr).

How common is ABHD4 p.Pro178Ser (c.532C>T) in the general population?

ABHD4 p.Pro178Ser (c.532C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ABHD4 p.Pro178Ser (c.532C>T)?

AlphaMissense predicts ambiguous (score 0.3928) — an in-silico prediction, not a clinical call.

ABHD4 p.Pro178Ser

c.532C>T · rs750231543 · VCV3131043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.3928	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -7.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,212 bp · p 0.74 · regional, not allelic
Overall
CADD	24.4	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 0.00267% African / African-American · 2/74,930 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,106 alleles · very rare

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: ABHD4
Protein: p.Pro178Ser
Coding: c.532C>T
MANE Select: NM_022060
dbSNP: rs750231543
Type: single nucleotide variant
Location: chr14:22603971 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30
Residue 178: the ab hydrolase-1 domain

Full ABHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD4 p.Pro178Leu Uncertain significance ★ ⚠ same residue
ABHD4 p.Ala230Glu Uncertain significance ★ ⚠ same type
ABHD4 p.Ala2Thr Uncertain significance ★ ⚠ same type
ABHD4 p.Arg115Lys Uncertain significance ★ ⚠ same type
ABHD4 p.Arg132Gln Uncertain significance ★ ⚠ same type
ABHD4 p.Arg185Cys Uncertain significance ★ ⚠ same type
ABHD4 p.Arg185His Uncertain significance ★ ⚠ same type
ABHD4 p.Arg200Cys 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/abhd4-p-pro178ser (accessed [today's date]).

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