Is ABHD16B p.Ala239Val (c.716C>T) pathogenic?

ABHD16B p.Ala239Val (c.716C>T) is classified Uncertain significance in ABHD16B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1055); Ultra-rare (popmax 0.0156%, eas).

How common is ABHD16B p.Ala239Val (c.716C>T) in the general population?

ABHD16B p.Ala239Val (c.716C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ABHD16B p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ABHD16B p.Ala239Val

c.716C>T · VCV3427519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -5.5
Regional constraint	o/e 1.06	unconstrained · MANE · 1,406 bp · p 0.089 · regional, not allelic
Overall
CADD	11.79	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 0.0156% East Asian · 7/44,858 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000868% 14/1,612,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,408
South Asian	0.0011%	90,990
European (non-Finnish)	0.000509%	196,623

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.Ala239Val
Coding: c.716C>T
MANE Select: NM_080622
Type: single nucleotide variant
Location: chr20:63862256 (GRCh38)
Gene constraint: LOEUF 1.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.64
Residue 239: the ab hydrolase-1 domain

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

Similar variants

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.Ala253Gly Uncertain significance ★ ⚠ same type
ABHD16B p.Ala253Val Uncertain significance ★ same type
ABHD16B p.Ala265Val 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-ala239val (accessed [today's date]).

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