Is ACP3 p.Pro157Ser (c.469C>T) pathogenic?

ACP3 p.Pro157Ser (c.469C>T) is classified Uncertain significance in ACP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely pathogenic (0.731); Very rare (popmax 0.00446%, eas).

How common is ACP3 p.Pro157Ser (c.469C>T) in the general population?

ACP3 p.Pro157Ser (c.469C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ACP3 p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely pathogenic (score 0.731) — an in-silico prediction, not a clinical call.

ACP3 p.Pro157Ser

c.469C>T · VCV3262477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.731	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Pangolin	Δ0.55	gain · loss 0.40 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 39 kb · p 0.9 · regional, not allelic
Overall
CADD	26.5	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 0.00446% East Asian · 2/44,796 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000412% 6/1,455,798 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00482%	20,749
East Asiangrpmax	0.00446%	22,398
South Asian	0.0011%	90,540

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACP3
Protein: p.Pro157Ser
Coding: c.469C>T
MANE Select: NM_001099
Type: single nucleotide variant
Location: chr3:132337468 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.51 · 17 PDB

Full ACP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP3 p.Asp301Glu Benign ★★ same type
ACP3 p.Ala116Ser Uncertain significance ★ ⚠ same type
ACP3 p.Ala121Ser Uncertain significance ★ ⚠ same type
ACP3 p.Ala311Thr Uncertain significance ★ ⚠ same type
ACP3 p.Ala4Thr Uncertain significance ★ ⚠ same type
ACP3 p.Ala9Thr Uncertain significance ★ ⚠ same type
ACP3 p.Arg111Gln Uncertain significance ★ ⚠ same type
ACP3 p.Arg111Trp 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/acp3-p-pro157ser (accessed [today's date]).

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