Is ABHD8 p.Cys11Ser (c.32G>C) pathogenic?

ABHD8 p.Cys11Ser (c.32G>C) is classified Uncertain significance in ABHD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: ambiguous (0.4836); Very rare (popmax 0.00172%, amr).

How common is ABHD8 p.Cys11Ser (c.32G>C) in the general population?

ABHD8 p.Cys11Ser (c.32G>C) is very rare (popmax 0.00172%, amr) (gnomAD).

What do computational predictors say about ABHD8 p.Cys11Ser (c.32G>C)?

AlphaMissense predicts ambiguous (score 0.4836) — an in-silico prediction, not a clinical call.

ABHD8 p.Cys11Ser

c.32G>C · rs746966639 · VCV2264210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4836	ambiguous
REVEL	0.278	benign-leaning
SaProt	LLR -4.14	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 527 bp · p 0.13 · regional, not allelic
Overall
CADD	23.6	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 0.00172% Admixed American · 1/58,146 alleles

Overall 0.00021% 3/1,429,826 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,146
Remaining individualsnot grpmax-eligible	0.00163%	61,242
European (non-Finnish)	8.59e-05%	1,163,854

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: ABHD8
Protein: p.Cys11Ser
Coding: c.32G>C
MANE Select: NM_024527
dbSNP: rs746966639
Type: single nucleotide variant
Location: chr19:17301585 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 79.84

Full ABHD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD8 p.Ala20= Benign ★★ same type
ABHD8 p.Ala136Thr Uncertain significance ★ ⚠ same type
ABHD8 p.Ala215Val Uncertain significance ★ ⚠ same type
ABHD8 p.Ala218Val Uncertain significance ★ ⚠ same type
ABHD8 p.Ala236Thr Uncertain significance ★ ⚠ same type
ABHD8 p.Ala319Asp Uncertain significance ★ ⚠ same type
ABHD8 p.Ala319Gly Uncertain significance ★ ⚠ same type
ABHD8 p.Ala426Pro 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/abhd8-p-cys11ser (accessed [today's date]).

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