Is ABHD16B p.Leu67Pro (c.200T>C) pathogenic?

ABHD16B p.Leu67Pro (c.200T>C) is classified Uncertain significance in ABHD16B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0527); Ultra-rare (popmax 0.0115%, nfe).

How common is ABHD16B p.Leu67Pro (c.200T>C) in the general population?

ABHD16B p.Leu67Pro (c.200T>C) is ultra-rare (popmax 0.0115%, nfe) (gnomAD).

What do computational predictors say about ABHD16B p.Leu67Pro (c.200T>C)?

AlphaMissense predicts likely benign (score 0.0527) — an in-silico prediction, not a clinical call.

ABHD16B p.Leu67Pro

c.200T>C · rs1277613288 · VCV2479568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0527	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -5.50	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 1.5	GERP -1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,406 bp · p 0.089 · regional, not allelic
Overall
CADD	12.8	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 0.0115% European (non-Finnish) · 126/1,092,468 alleles

Filtering AF 0.00984% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00924%

Overall 0.00907% 128/1,410,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0115%	8,670
Remaining individualsnot grpmax-eligible	0.00372%	26,871

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.Leu67Pro
Coding: c.200T>C
MANE Select: NM_080622
dbSNP: rs1277613288
Type: single nucleotide variant
Location: chr20:63861740 (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-leu67pro (accessed [today's date]).

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