Is ACYP2 p.Arg98Thr (c.293G>C) pathogenic?

ACYP2 p.Arg98Thr (c.293G>C) is classified Uncertain significance in ACYP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.5081); Very rare (popmax 0.00168%, amr).

How common is ACYP2 p.Arg98Thr (c.293G>C) in the general population?

ACYP2 p.Arg98Thr (c.293G>C) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about ACYP2 p.Arg98Thr (c.293G>C)?

AlphaMissense predicts ambiguous (score 0.5081) — an in-silico prediction, not a clinical call.

ACYP2 p.Arg98Thr

c.293G>C · VCV4003437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5081	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -12.71	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.8, phastCons 1
Overall
CADD	24.9	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 0.00168% Admixed American · 1/59,580 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000284% 4/1,409,342 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,580
Remaining individualsnot grpmax-eligible	0.00165%	60,622
European (non-Finnish)	0.000176%	567,943

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: ACYP2
Protein: p.Arg98Thr
Coding: c.293G>C
MANE Select: NM_138448
Type: single nucleotide variant
Location: chr2:54304795 (GRCh38)
Gene constraint: LOEUF 1.728 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 95.94
Residue 98: the acylphosphatase-like domain

Full ACYP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACYP2 p.Arg98Lys Uncertain significance ★ ⚠ same residue
TSPYL6 p.Ala100= Benign ★★ same type
TSPYL6 p.Ala60Val Benign ★★ same type
TSPYL6 p.Asp149= Benign ★★ same type
TSPYL6 p.Glu96Asp Benign ★★ same type
TSPYL6 p.Met1Val Benign ★★ same type
TSPYL6 p.Pro20= Benign ★★ same type
TSPYL6 p.Pro4Leu Benign ★★ 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/acyp2-p-arg98thr (accessed [today's date]).

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