Is ABHD1 p.Ser57Pro (c.169T>C) pathogenic?

ABHD1 p.Ser57Pro (c.169T>C) is classified Likely benign in ABHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.052); Ultra-rare (popmax 0.0559%, eas).

How common is ABHD1 p.Ser57Pro (c.169T>C) in the general population?

ABHD1 p.Ser57Pro (c.169T>C) is ultra-rare (popmax 0.0559%, eas) (gnomAD).

What do computational predictors say about ABHD1 p.Ser57Pro (c.169T>C)?

AlphaMissense predicts likely benign (score 0.052) — an in-silico prediction, not a clinical call.

ABHD1 p.Ser57Pro

c.169T>C · rs766954604 · VCV3130017

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.052 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.052	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -1.98	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 2.7	GERP 0.23, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 6,792 bp · p 0.038 · regional, not allelic
Overall
CADD	14.01	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 0.0559% East Asian · 25/44,740 alleles

Filtering AF 0.0388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.00155% 25/1,611,898 alleles · ultra-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: ABHD1
Protein: p.Ser57Pro
Coding: c.169T>C
MANE Select: NM_032604
dbSNP: rs766954604
Type: single nucleotide variant
Location: chr2:27128495 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.75

Full ABHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD1 p.Ser57Phe Uncertain significance ★ ⚠ same residue
ABHD1 p.Ala154Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala172Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala326Glu Uncertain significance ★ ⚠ same type
ABHD1 p.Ala336Val Uncertain significance ★ ⚠ same type
ABHD1 p.Ala349Val Uncertain significance ★ ⚠ same type
ABHD1 p.Ala381Thr Uncertain significance ★ ⚠ same type
ABHD1 p.Ala50Val 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/abhd1-p-ser57pro (accessed [today's date]).

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