Is ACP6 p.Tyr287Cys (c.860A>G) pathogenic?

ACP6 p.Tyr287Cys (c.860A>G) is classified Uncertain significance in ACP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1042); Very rare (popmax 0.00133%, afr).

How common is ACP6 p.Tyr287Cys (c.860A>G) in the general population?

ACP6 p.Tyr287Cys (c.860A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ACP6 p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

ACP6 p.Tyr287Cys

c.860A>G · VCV4636916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -7.17	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 1.8	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.055 · regional, not allelic
Overall
CADD	20.1	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 0.00133% African / African-American · 1/74,936 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,814 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,936
European (non-Finnish)	0.000932%	107,271

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: ACP6
Protein: p.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_016361
Type: single nucleotide variant
Location: chr1:147652470 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.22 · 3 PDB
Residue 287: an α-helix

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-tyr287cys (accessed [today's date]).

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