Is ABHD6 p.Arg65Trp (c.193C>T) pathogenic?

ABHD6 p.Arg65Trp (c.193C>T) is classified Uncertain significance in ABHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.7257); Very rare (popmax 0.00661%, nfe).

How common is ABHD6 p.Arg65Trp (c.193C>T) in the general population?

ABHD6 p.Arg65Trp (c.193C>T) is very rare (popmax 0.00661%, nfe) (gnomAD).

What do computational predictors say about ABHD6 p.Arg65Trp (c.193C>T)?

AlphaMissense predicts likely pathogenic (score 0.7257) — an in-silico prediction, not a clinical call.

ABHD6 p.Arg65Trp

c.193C>T · VCV3993173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7257	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -12.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.038 · regional, not allelic
Overall
CADD	32.0	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 0.00661% European (non-Finnish) · 78/1,180,024 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00527% 85/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,129
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.00329%	30,361

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: ABHD6
Protein: p.Arg65Trp
Coding: c.193C>T
MANE Select: NM_001320126
Type: single nucleotide variant
Location: chr3:58267262 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 65: a β-strand

Full ABHD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD6 p.Ala12Val Uncertain significance ★ ⚠ same type
ABHD6 p.Ala158Asp Uncertain significance ★ ⚠ same type
ABHD6 p.Ala196Thr Uncertain significance ★ ⚠ same type
ABHD6 p.Ala82Asp Uncertain significance ★ ⚠ same type
ABHD6 p.Arg221Cys Uncertain significance ★ ⚠ same type
ABHD6 p.Arg236His Uncertain significance ★ ⚠ same type
ABHD6 p.Arg244Gln Uncertain significance ★ ⚠ same type
ABHD6 p.Arg51His 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/abhd6-p-arg65trp (accessed [today's date]).

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