Is ABHD15 p.Pro366Ser (c.1096C>T) pathogenic?

ABHD15 p.Pro366Ser (c.1096C>T) is classified Uncertain significance in ABHD15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1478); Very rare (popmax 0.00333%, amr).

How common is ABHD15 p.Pro366Ser (c.1096C>T) in the general population?

ABHD15 p.Pro366Ser (c.1096C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABHD15 p.Pro366Ser (c.1096C>T)?

AlphaMissense predicts likely benign (score 0.1478) — an in-silico prediction, not a clinical call.

ABHD15 p.Pro366Ser

c.1096C>T · VCV4159214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1478 · 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	0.1478	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -9.52	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 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,402 bp · p 0.8 · regional, not allelic
Overall
CADD	23.4	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 · 2/60,016 alleles

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

Overall 0.000547% 8/1,461,830 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,008
East Asian	0.00223%	44,880
European (non-Finnish)	0.000424%	236,002

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: ABHD15
Protein: p.Pro366Ser
Coding: c.1096C>T
MANE Select: NM_198147
Type: single nucleotide variant
Location: chr17:29562872 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.70

Full ABHD15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD15 p.Pro366Leu Uncertain significance ★ ⚠ same residue
ABHD15 p.Ala16Pro Uncertain significance ★ ⚠ same type
ABHD15 p.Ala228Val Uncertain significance ★ ⚠ same type
ABHD15 p.Ala229Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala233Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala260Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala291Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala358Pro 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/abhd15-p-pro366ser (accessed [today's date]).

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