Is ACYP2 p.Ala4Thr (c.10G>A) pathogenic?

ACYP2 p.Ala4Thr (c.10G>A) is classified Uncertain significance in ACYP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.0816); Ultra-rare (popmax 0.0165%, mid).

How common is ACYP2 p.Ala4Thr (c.10G>A) in the general population?

ACYP2 p.Ala4Thr (c.10G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ACYP2 p.Ala4Thr (c.10G>A)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

ACYP2 p.Ala4Thr

c.10G>A · VCV4637240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -6.21	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 3.1	GERP -0.97, phastCons 0.6
Overall
CADD	8.219	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 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0058%

Overall 0.00103% 15/1,460,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
Admixed American	0.015%	6,653
Remaining individualsnot grpmax-eligible	0.0016%	62,452
South Asian	0.0011%	90,638
European (non-Finnish)	0.000254%	393,147

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.Ala4Thr
Coding: c.10G>A
MANE Select: NM_138448
Type: single nucleotide variant
Location: chr2:54115708 (GRCh38)
Gene constraint: LOEUF 1.728 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 95.94

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

Similar variants

TSPYL6 p.Pro4Leu Benign ★★ same residue
TSPYL6 p.Pro4Gln 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

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-ala4thr (accessed [today's date]).

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