Is ABHD15 p.Ala16Pro (c.46G>C) pathogenic?

ABHD15 p.Ala16Pro (c.46G>C) is classified Uncertain significance in ABHD15 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.1615); Absent from gnomAD v4.1.

How common is ABHD15 p.Ala16Pro (c.46G>C) in the general population?

ABHD15 p.Ala16Pro (c.46G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABHD15 p.Ala16Pro (c.46G>C)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

ABHD15 p.Ala16Pro

c.46G>C · rs2508403361 · VCV2647615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -11.69	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
Conservation	phyloP 1.6	GERP 0.94, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 4,402 bp · p 0.8 · regional, not allelic
Overall
CADD	15.47	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABHD15
Protein: p.Ala16Pro
Coding: c.46G>C
MANE Select: NM_198147
dbSNP: rs2508403361
Type: single nucleotide variant
Location: chr17:29566921 (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.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
ABHD15 p.Ala444Ser Uncertain significance ★ ⚠ same type
ABHD15 p.Ala6Val 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-ala16pro (accessed [today's date]).

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