Is ABHD3 p.Thr273= (c.819C>T) pathogenic?

ABHD3 p.Thr273= (c.819C>T) is classified Benign in ABHD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). Common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele.

ABHD3 p.Thr273=

Q: How common is ABHD3 p.Thr273= (c.819C>T) in the general population?

ABHD3 p.Thr273= (c.819C>T) is common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.819C>T · rs61729089 · VCV775465

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.021	GERP -3.3, phastCons 0.24
Overall
CADD	5.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.3% African / African-American · 3,976/74,966 alleles

Filtering AF 5.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.11%

Overall 0.28% 4,518/1,613,514 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.3%	19
Middle Eastern	0.413%	242
Admixed American	0.342%	292
Remaining individualsnot grpmax-eligible	0.338%	296
South Asian	0.0088%	11,363
European (non-Finnish)	0.00788%	12,687

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.Thr273=
Coding: c.819C>T
MANE Select: NM_138340
dbSNP: rs61729089
Type: single nucleotide variant
Location: chr18:21659193 (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.Ala43Val Uncertain significance ★ ⚠ same type
ABHD3 p.Ala45Ser Uncertain significance ★ ⚠ same type
ABHD3 p.Arg108Met 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-thr273 (accessed [today's date]).

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