Is ACP1 p.Thr141= (c.423G>A) pathogenic?

ACP1 p.Thr141= (c.423G>A) is classified Benign in ACP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-15). Rare (popmax 0.377%, nfe).

How common is ACP1 p.Thr141= (c.423G>A) in the general population?

ACP1 p.Thr141= (c.423G>A) is rare (popmax 0.377%, nfe) (gnomAD).

ACP1 p.Thr141=

c.423G>A · rs55709515 · VCV711059

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.377%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor loss, 23 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.7	GERP -4.7
Overall
CADD	7.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.377% European (non-Finnish) · 4,449/1,180,006 alleles

Filtering AF 0.368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.364%

Overall 0.416% 6,718/1,613,706 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.05%	33
European (non-Finnish)grpmax	0.377%	265
Amishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.322%	311
Admixed American	0.117%	857
African / African-American	0.0506%	1,975
Middle Eastern	0.0175%	5,706
South Asian	0.00549%	18,214
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

Finnish 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: ACP1
Protein: p.Thr141=
Coding: c.423G>A
MANE Select: NM_004300
dbSNP: rs55709515
Type: single nucleotide variant
Location: chr2:277250 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.16 · 17 PDB
Residue 141: an α-helix

Full ACP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP1 c.43+10C>T Benign ★★ same type
ACP1 c.43+8G>A Benign ★★ same type
ACP1 p.Gly134= Benign ★★ same type
ACP1 p.Lys7Asn Benign ★★ ⚠ same type
ACP1 c.231+100G>T Uncertain significance ★ same type
ACP1 c.231+49T>C Uncertain significance ★ same type
ACP1 c.231+57G>A Uncertain significance ★ same type
ACP1 c.231+73G>A 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/acp1-p-thr141 (accessed [today's date]).

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