Is ABHD2 p.Pro60Arg (c.179C>G) pathogenic?

ABHD2 p.Pro60Arg (c.179C>G) is classified Uncertain significance in ABHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2235); Ultra-rare (popmax 0.056%, afr).

How common is ABHD2 p.Pro60Arg (c.179C>G) in the general population?

ABHD2 p.Pro60Arg (c.179C>G) is ultra-rare (popmax 0.056%, afr) (gnomAD).

What do computational predictors say about ABHD2 p.Pro60Arg (c.179C>G)?

AlphaMissense predicts likely benign (score 0.2235) — an in-silico prediction, not a clinical call.

ABHD2 p.Pro60Arg

c.179C>G · rs141982781 · VCV2467708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2235	likely benign
REVEL	0.414	indeterminate
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL 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 0.74	unconstrained · MANE · 79 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	28.6	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 0.056% African / African-American · 42/75,056 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00328% 53/1,613,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.056%	1,787
Admixed American	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0016%	62,492
South Asian	0.0011%	91,034
European (non-Finnish)	8.48e-05%	1,179,768

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: ABHD2
Protein: p.Pro60Arg
Coding: c.179C>G
MANE Select: NM_152924
dbSNP: rs141982781
Type: single nucleotide variant
Location: chr15:89116506 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 91.06

Full ABHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD2 p.His312= Benign ★★ same type
ABHD2 p.Tyr400= Benign ★★ same type
ABHD2 p.Val420= Benign ★★ same type
ABHD2 p.Ala222Gly Uncertain significance ★ ⚠ same type
ABHD2 p.Ala274Thr Uncertain significance ★ ⚠ same type
ABHD2 p.Arg175Cys Uncertain significance ★ ⚠ same type
ABHD2 p.Arg254Gln Uncertain significance ★ ⚠ same type
ABHD2 p.Arg293Gln 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/abhd2-p-pro60arg (accessed [today's date]).

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