Is ABHD17A p.Thr34Pro (c.100A>C) pathogenic?

ABHD17A p.Thr34Pro (c.100A>C) is classified Uncertain significance in ABHD17A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.8779); Very rare (popmax 0.00134%, afr).

How common is ABHD17A p.Thr34Pro (c.100A>C) in the general population?

ABHD17A p.Thr34Pro (c.100A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ABHD17A p.Thr34Pro (c.100A>C)?

AlphaMissense predicts likely pathogenic (score 0.8779) — an in-silico prediction, not a clinical call.

ABHD17A p.Thr34Pro

c.100A>C · rs1366181741 · VCV3130767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8779	likely pathogenic
REVEL	0.357	indeterminate
SaProt	LLR -14.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,565 bp · p 0.0021 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00134% African / African-American · 1/74,766 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00025% 4/1,602,176 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,766
European (non-Finnish)	0.000255%	392,696

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.Thr34Pro
Coding: c.100A>C
MANE Select: NM_001130111
dbSNP: rs1366181741
Type: single nucleotide variant
Location: chr19:1881467 (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-thr34pro (accessed [today's date]).

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