Is ABHD17A p.Pro39Arg (c.116C>G) pathogenic?

ABHD17A p.Pro39Arg (c.116C>G) is classified Uncertain significance in ABHD17A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.1471); Ultra-rare (popmax 0.0451%, mid).

How common is ABHD17A p.Pro39Arg (c.116C>G) in the general population?

ABHD17A p.Pro39Arg (c.116C>G) is ultra-rare (popmax 0.0451%, mid) (gnomAD).

What do computational predictors say about ABHD17A p.Pro39Arg (c.116C>G)?

AlphaMissense predicts likely benign (score 0.1471) — an in-silico prediction, not a clinical call.

ABHD17A p.Pro39Arg

c.116C>G · VCV3992868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1471 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1471	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Pangolin	Δ0.34	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.3	GERP -2.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,565 bp · p 0.0021 · regional, not allelic
Overall
CADD	22.4	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 0.0451% Middle Eastern · 2/4,430 alleles

Filtering AF 0.008% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00335%

Overall 0.000811% 13/1,603,244 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0451%	2,215
Remaining individualsnot grpmax-eligible	0.00483%	20,698
South Asian	0.0033%	30,289
European (non-Finnish)	0.000424%	235,700

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: ABHD17A
Protein: p.Pro39Arg
Coding: c.116C>G
MANE Select: NM_001130111
Type: single nucleotide variant
Location: chr19:1881451 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 89.99

Full ABHD17A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD17A c.332+230G>A Uncertain significance ★ same type
ABHD17A c.332+239C>G Uncertain significance ★ same type
ABHD17A c.332+243G>A Uncertain significance ★ same type
ABHD17A c.332+261C>G Uncertain significance ★ same type
ABHD17A c.332+261C>T Uncertain significance ★ same type
ABHD17A c.332+306C>T Uncertain significance ★ same type
ABHD17A p.Ala168Thr Uncertain significance ★ ⚠ same type
ABHD17A p.Ala273Thr 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/abhd17a-p-pro39arg (accessed [today's date]).

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