Is ACP6 p.Met8Val (c.22A>G) pathogenic?

ACP6 p.Met8Val (c.22A>G) is classified Likely benign in ACP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.057); Ultra-rare (popmax 0.0533%, mid).

How common is ACP6 p.Met8Val (c.22A>G) in the general population?

ACP6 p.Met8Val (c.22A>G) is ultra-rare (popmax 0.0533%, mid) (gnomAD).

What do computational predictors say about ACP6 p.Met8Val (c.22A>G)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

ACP6 p.Met8Val

c.22A>G · rs1462870297 · VCV2382597

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.21	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 -3.3	GERP -4.3
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.055 · regional, not allelic
Overall
CADD	0.208	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 0.0533% Middle Eastern · 3/5,632 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00772%

Overall 0.000844% 13/1,539,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0533%	1,877
Remaining individualsnot grpmax-eligible	0.00672%	14,890
Finnishnot grpmax-eligible	0.00178%	56,082
European (non-Finnish)	0.000438%	228,152

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.Met8Val
Coding: c.22A>G
MANE Select: NM_016361
dbSNP: rs1462870297
Type: single nucleotide variant
Location: chr1:147670027 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.22 · 3 PDB

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-met8val (accessed [today's date]).

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