Is ABHD5 p.Ter350= (c.1049G>A) pathogenic?

ABHD5 p.Ter350= (c.1049G>A) is classified Likely benign in ABHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). Ultra-rare (popmax 0.0424%, eas).

How common is ABHD5 p.Ter350= (c.1049G>A) in the general population?

ABHD5 p.Ter350= (c.1049G>A) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

ABHD5 p.Ter350=

c.1049G>A · rs575959466 · VCV2175572

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.9, phastCons 1
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,854 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00118% 19/1,613,900 alleles · ultra-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.Ter350=
Coding: c.1049G>A
MANE Select: NM_016006
dbSNP: rs575959466
Type: single nucleotide variant
Location: chr3:43718531 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.62

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-ter350 (accessed [today's date]).

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