Is ACP6 p.Ile166Val (c.496A>G) pathogenic?

ACP6 p.Ile166Val (c.496A>G) is classified Uncertain significance in ACP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). AlphaMissense: likely benign (0.1328); Absent from gnomAD v4.1.

How common is ACP6 p.Ile166Val (c.496A>G) in the general population?

ACP6 p.Ile166Val (c.496A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACP6 p.Ile166Val (c.496A>G)?

AlphaMissense predicts likely benign (score 0.1328) — an in-silico prediction, not a clinical call.

ACP6 p.Ile166Val

c.496A>G · VCV3999909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1328	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -4.76	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 3.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.055 · regional, not allelic
Overall
CADD	21.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACP6
Protein: p.Ile166Val
Coding: c.496A>G
MANE Select: NM_016361
Type: single nucleotide variant
Location: chr1:147659023 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.22 · 3 PDB
Residue 166: the 'substrate binding' region

Full ACP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP6 p.Arg218Trp Benign ★★ ⚠ same type
ACP6 p.Leu224= Benign ★★ same type
ACP6 p.Val127Met Likely pathogenic ★ ⚠ same type
ACP6 p.Ala196Glu Uncertain significance ★ ⚠ same type
ACP6 p.Ala257Thr Uncertain significance ★ ⚠ same type
ACP6 p.Ala356Thr Uncertain significance ★ ⚠ same type
ACP6 p.Ala61Gly Uncertain significance ★ ⚠ same type
ACP6 p.Arg140Lys 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/acp6-p-ile166val (accessed [today's date]).

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