Is ABHD5 p.Arg56His (c.167G>A) pathogenic?

ABHD5 p.Arg56His (c.167G>A) is classified Uncertain significance in ABHD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-09). AlphaMissense: likely benign (0.0644); Ultra-rare (popmax 0.0167%, mid).

How common is ABHD5 p.Arg56His (c.167G>A) in the general population?

ABHD5 p.Arg56His (c.167G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ABHD5 p.Arg56His (c.167G>A)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

ABHD5 p.Arg56His

c.167G>A · rs757742884 · VCV1901627

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -4.78	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 -0.64	GERP -5.5
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.24 · regional, not allelic
Overall
CADD	6.317	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 0.0167% Middle Eastern · 1/5,986 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00556%

Overall 0.00226% 36/1,592,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,986
African / African-American	0.0135%	7,394
Admixed American	0.00692%	14,461
South Asian	0.00563%	17,746
Remaining individualsnot grpmax-eligible	0.00326%	30,715
European (non-Finnish)	0.0012%	83,311

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.Arg56His
Coding: c.167G>A
MANE Select: NM_016006
dbSNP: rs757742884
Type: single nucleotide variant
Location: chr3:43702248 (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.Asp12Asn Uncertain significance ★★ ⚠ same type
ABHD5 p.Cys140Gly 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-arg56his (accessed [today's date]).

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