Is ACP4 p.Pro307Leu (c.920C>T) pathogenic?

ACP4 p.Pro307Leu (c.920C>T) is classified Uncertain significance in ACP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.4048); Very rare (popmax 0.0011%, sas).

How common is ACP4 p.Pro307Leu (c.920C>T) in the general population?

ACP4 p.Pro307Leu (c.920C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ACP4 p.Pro307Leu (c.920C>T)?

AlphaMissense predicts ambiguous (score 0.4048) — an in-silico prediction, not a clinical call.

ACP4 p.Pro307Leu

c.920C>T · rs1175084656 · VCV3138961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.4048	ambiguous
REVEL	0.476	indeterminate
SaProt	LLR -9.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 4,740 bp · p 0.54 · regional, not allelic
Overall
CADD	25.8	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 0.0011% South Asian · 1/91,082 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000806% 13/1,613,858 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.00102%	98,335

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: ACP4
Protein: p.Pro307Leu
Coding: c.920C>T
MANE Select: NM_033068
dbSNP: rs1175084656
Type: single nucleotide variant
Location: chr19:50794515 (GRCh38)
Gene constraint: LOEUF 1.413 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30
Residue 307: a disulfide bond

Full ACP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP4 p.Arg111Cys Pathogenic/Likely pathogenic ★★ same type
ACP4 c.550-4C>T Benign ★★ same type
ACP4 c.550-9C>T Benign ★★ same type
ACP4 p.Gly328Ala Benign ★★ same type
ACP4 p.Pro125= Benign ★★ same type
ACP4 c.645+1G>A Likely pathogenic ★ same type
ACP4 p.Leu85Pro Pathogenic ★ same type
ACP4 p.Met282Thr Pathogenic ★ ⚠ 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/acp4-p-pro307leu (accessed [today's date]).

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