Is ABHD5 p.Ala161Val (c.482C>T) pathogenic?

ABHD5 p.Ala161Val (c.482C>T) is classified Uncertain significance in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: ambiguous (0.4182); Very rare (popmax 0.000254%, nfe).

How common is ABHD5 p.Ala161Val (c.482C>T) in the general population?

ABHD5 p.Ala161Val (c.482C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ABHD5 p.Ala161Val (c.482C>T)?

AlphaMissense predicts ambiguous (score 0.4182) — an in-silico prediction, not a clinical call.

ABHD5 p.Ala161Val

c.482C>T · rs2084557528 · VCV1916112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4182	ambiguous
REVEL	0.557	indeterminate
SaProt	LLR -9.03	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	25.5	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 0.000254% European (non-Finnish) · 3/1,180,042 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,880 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: ABHD5
Protein: p.Ala161Val
Coding: c.482C>T
MANE Select: NM_016006
dbSNP: rs2084557528
Type: single nucleotide variant
Location: chr3:43702563 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62
Residue 161: the ab hydrolase-1 domain

Full ABHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD5 c.133+1G>A Likely pathogenic ★★ same type
ABHD5 c.507-1G>A Pathogenic ★★ same type
ABHD5 p.Arg184Ter Pathogenic ★★ same type
ABHD5 p.Arg234Ter Pathogenic ★★ same type
ABHD5 p.Arg280Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Glu336Ter Pathogenic/Likely pathogenic ★★ same type
ABHD5 p.Arg56His Uncertain significance ★★ ⚠ same type
ABHD5 p.Asp12Asn 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/abhd5-p-ala161val (accessed [today's date]).

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