Is ABHD3 p.Arg108Met (c.323G>T) pathogenic?

ABHD3 p.Arg108Met (c.323G>T) is classified Uncertain significance in ABHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: ambiguous (0.5545); Very rare (popmax 0.000256%, nfe).

How common is ABHD3 p.Arg108Met (c.323G>T) in the general population?

ABHD3 p.Arg108Met (c.323G>T) is very rare (popmax 0.000256%, nfe) (gnomAD).

What do computational predictors say about ABHD3 p.Arg108Met (c.323G>T)?

AlphaMissense predicts ambiguous (score 0.5545) — an in-silico prediction, not a clinical call.

ABHD3 p.Arg108Met

c.323G>T · VCV4164501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5545	ambiguous
REVEL	0.63	indeterminate
SaProt	LLR -14.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 53 kb · p 0.73 · regional, not allelic
Overall
CADD	31.0	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 0.000256% European (non-Finnish) · 3/1,173,904 alleles

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

Overall 0.000206% 3/1,454,262 alleles · very 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: ABHD3
Protein: p.Arg108Met
Coding: c.323G>T
MANE Select: NM_138340
Type: single nucleotide variant
Location: chr18:21703587 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39

Full ABHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD3 p.Pro187Thr Uncertain significance ★★ ⚠ same type
ABHD3 p.Thr273= Benign ★★ same type
ABHD3 p.Ala43Val Uncertain significance ★ ⚠ same type
ABHD3 p.Ala45Ser Uncertain significance ★ ⚠ same type
ABHD3 p.Arg170Ser Uncertain significance ★ ⚠ same type
ABHD3 p.Arg177Lys Uncertain significance ★ ⚠ same type
ABHD3 p.Arg307Gln Uncertain significance ★ ⚠ same type
ABHD3 p.Asp126Asn 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/abhd3-p-arg108met (accessed [today's date]).

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