Is ACYP2 p.Ile34Val (c.100A>G) pathogenic?

ACYP2 p.Ile34Val (c.100A>G) is classified Uncertain significance in ACYP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0925); Very rare (popmax 0.000169%, nfe).

How common is ACYP2 p.Ile34Val (c.100A>G) in the general population?

ACYP2 p.Ile34Val (c.100A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ACYP2 p.Ile34Val (c.100A>G)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

ACYP2 p.Ile34Val

c.100A>G · VCV4637241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.71	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 2	GERP -5, phastCons 0.047
Overall
CADD	14.08	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 0.000169% European (non-Finnish) · 2/1,179,980 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,942 alleles · very 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: ACYP2
Protein: p.Ile34Val
Coding: c.100A>G
MANE Select: NM_138448
Type: single nucleotide variant
Location: chr2:54138663 (GRCh38)
Gene constraint: LOEUF 1.728 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 95.94
Residue 34: the acylphosphatase-like domain

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

Similar variants

ACYP2 p.Ile34Met 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-ile34val (accessed [today's date]).

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