Is ACP4 p.Ser271Pro (c.811T>C) pathogenic?

ACP4 p.Ser271Pro (c.811T>C) is classified Uncertain significance in ACP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: ambiguous (0.5272); Very rare (popmax 0.000424%, nfe).

How common is ACP4 p.Ser271Pro (c.811T>C) in the general population?

ACP4 p.Ser271Pro (c.811T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ACP4 p.Ser271Pro (c.811T>C)?

AlphaMissense predicts ambiguous (score 0.5272) — an in-silico prediction, not a clinical call.

ACP4 p.Ser271Pro

c.811T>C · VCV4217849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5272 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5272	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -13.59	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 4,740 bp · p 0.54 · regional, not allelic
Overall
CADD	26.3	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 0.000424% European (non-Finnish) · 5/1,180,036 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,014 alleles · very rare

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.Ser271Pro
Coding: c.811T>C
MANE Select: NM_033068
Type: single nucleotide variant
Location: chr19:50793920 (GRCh38)
Gene constraint: LOEUF 1.413 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30
Residue 271: 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-ser271pro (accessed [today's date]).

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