Is ACP6 p.Pro152Ser (c.454C>T) pathogenic?

ACP6 p.Pro152Ser (c.454C>T) is classified Uncertain significance in ACP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.0797); Very rare (popmax 0.00267%, afr).

How common is ACP6 p.Pro152Ser (c.454C>T) in the general population?

ACP6 p.Pro152Ser (c.454C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ACP6 p.Pro152Ser (c.454C>T)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

ACP6 p.Pro152Ser

c.454C>T · VCV3481946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.88	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 6.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.055 · regional, not allelic
Overall
CADD	17.99	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 0.00267% African / African-American · 2/74,922 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,461
European (non-Finnish)	8.47e-05%	1,180,027

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.Pro152Ser
Coding: c.454C>T
MANE Select: NM_016361
Type: single nucleotide variant
Location: chr1:147659421 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.22 · 3 PDB
Residue 152: the 'substrate binding' region; a β-strand

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-pro152ser (accessed [today's date]).

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