Is ABHD16B p.Arg293Cys (c.877C>T) pathogenic?

ABHD16B p.Arg293Cys (c.877C>T) is classified Uncertain significance in ABHD16B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.1324); Very rare (popmax 0.00269%, afr).

How common is ABHD16B p.Arg293Cys (c.877C>T) in the general population?

ABHD16B p.Arg293Cys (c.877C>T) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about ABHD16B p.Arg293Cys (c.877C>T)?

AlphaMissense predicts likely benign (score 0.1324) — an in-silico prediction, not a clinical call.

ABHD16B p.Arg293Cys

c.877C>T · VCV3320861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1324	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -10.03	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 4.8	GERP -2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,406 bp · p 0.089 · regional, not allelic
Overall
CADD	28.8	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 0.00269% African / African-American · 2/74,436 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000908%

Overall 0.00151% 24/1,586,106 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,218
European (non-Finnish)	0.00171%	58,462
Remaining individualsnot grpmax-eligible	0.00163%	61,512
South Asian	0.00113%	88,412

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: ABHD16B
Protein: p.Arg293Cys
Coding: c.877C>T
MANE Select: NM_080622
Type: single nucleotide variant
Location: chr20:63862417 (GRCh38)
Gene constraint: LOEUF 1.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.64
Residue 293: the ab hydrolase-1 domain

Full ABHD16B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD16B p.Arg293His Uncertain significance ★ ⚠ same residue
ABHD16B p.Ala143Pro Uncertain significance ★ ⚠ same type
ABHD16B p.Ala147Gly Uncertain significance ★ ⚠ same type
ABHD16B p.Ala181Thr Uncertain significance ★ ⚠ same type
ABHD16B p.Ala195Thr Uncertain significance ★ ⚠ same type
ABHD16B p.Ala20Ser Uncertain significance ★ ⚠ same type
ABHD16B p.Ala239Val Uncertain significance ★ ⚠ same type
ABHD16B p.Ala253Gly 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/abhd16b-p-arg293cys (accessed [today's date]).

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