Is CPSF2 p.Asp43Asn (c.127G>A) pathogenic?

CPSF2 p.Asp43Asn (c.127G>A) is classified Uncertain significance in CPSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1141); Absent from gnomAD v4.1.

How common is CPSF2 p.Asp43Asn (c.127G>A) in the general population?

CPSF2 p.Asp43Asn (c.127G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF2 p.Asp43Asn (c.127G>A)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

CPSF2 p.Asp43Asn

c.127G>A · VCV4233557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.98	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 12 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	23.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPSF2
Protein: p.Asp43Asn
Coding: c.127G>A
MANE Select: NM_017437
Type: single nucleotide variant
Location: chr14:92131111 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 6 PDB
Residue 43: a turn

Full CPSF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF2 p.Ala267Val Uncertain significance ★ ⚠ same type
CPSF2 p.Arg105Gln Uncertain significance ★ ⚠ same type
CPSF2 p.Arg366Cys Uncertain significance ★ ⚠ same type
CPSF2 p.Arg366His Uncertain significance ★ ⚠ same type
CPSF2 p.Arg449His Uncertain significance ★ ⚠ same type
CPSF2 p.Arg534Gln Uncertain significance ★ ⚠ same type
CPSF2 p.Arg579His Uncertain significance ★ ⚠ same type
CPSF2 p.Arg730Gln 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/cpsf2-p-asp43asn (accessed [today's date]).

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