Is ACP3 p.Phe24Ser (c.71T>C) pathogenic?

ACP3 p.Phe24Ser (c.71T>C) is classified Uncertain significance in ACP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0825); Very rare (popmax 0.00407%, nfe).

How common is ACP3 p.Phe24Ser (c.71T>C) in the general population?

ACP3 p.Phe24Ser (c.71T>C) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about ACP3 p.Phe24Ser (c.71T>C)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

ACP3 p.Phe24Ser

c.71T>C · rs138177825 · VCV3138837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -5.40	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 -0.18	GERP -1
Regional constraint	o/e 1.01	unconstrained · MANE · 39 kb · p 0.9 · regional, not allelic
Overall
CADD	15.82	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 0.00407% European (non-Finnish) · 48/1,179,876 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00328% 53/1,613,730 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,581
Admixed American	0.00333%	29,986
Remaining individualsnot grpmax-eligible	0.0032%	31,230
African / African-American	0.00133%	74,928

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.Phe24Ser
Coding: c.71T>C
MANE Select: NM_001099
dbSNP: rs138177825
Type: single nucleotide variant
Location: chr3:132317527 (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-phe24ser (accessed [today's date]).

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