Is ABHD16B p.Arg319Ser (c.955C>A) pathogenic?

ABHD16B p.Arg319Ser (c.955C>A) is classified Uncertain significance in ABHD16B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely pathogenic (0.9181); Very rare (popmax 0.00233%, eas).

How common is ABHD16B p.Arg319Ser (c.955C>A) in the general population?

ABHD16B p.Arg319Ser (c.955C>A) is very rare (popmax 0.00233%, eas) (gnomAD).

What do computational predictors say about ABHD16B p.Arg319Ser (c.955C>A)?

AlphaMissense predicts likely pathogenic (score 0.9181) — an in-silico prediction, not a clinical call.

ABHD16B p.Arg319Ser

c.955C>A · rs777198719 · VCV2335420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9181	likely pathogenic · top 1% in ABHD16B
REVEL	0.334	indeterminate
SaProt	LLR -15.05	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 4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,406 bp · p 0.089 · regional, not allelic
Overall
CADD	23.6	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 0.00233% East Asian · 1/42,876 alleles

Overall 0.000657% 1/152,236 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: ABHD16B
Protein: p.Arg319Ser
Coding: c.955C>A
MANE Select: NM_080622
dbSNP: rs777198719
Type: single nucleotide variant
Location: chr20:63862495 (GRCh38)
Gene constraint: LOEUF 1.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.64

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.Ala239Val Uncertain significance ★ ⚠ same type
ABHD16B p.Ala253Gly Uncertain significance ★ ⚠ same type
ABHD16B p.Ala253Val 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-arg319ser (accessed [today's date]).

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