Is CPSF2 p.Ala267Val (c.800C>T) pathogenic?

CPSF2 p.Ala267Val (c.800C>T) is classified Uncertain significance in CPSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). AlphaMissense: ambiguous (0.4257); Absent from gnomAD v4.1.

How common is CPSF2 p.Ala267Val (c.800C>T) in the general population?

CPSF2 p.Ala267Val (c.800C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF2 p.Ala267Val (c.800C>T)?

AlphaMissense predicts ambiguous (score 0.4257) — an in-silico prediction, not a clinical call.

CPSF2 p.Ala267Val

c.800C>T · rs2545220390 · VCV3076887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4257 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,858)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4257	ambiguous
REVEL	0.228	benign-leaning
SaProt	LLR -8.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 12 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	22.4	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

No allele count reported in gnomAD v4.1 (AN 1,613,858). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPSF2
Protein: p.Ala267Val
Coding: c.800C>T
MANE Select: NM_017437
dbSNP: rs2545220390
Type: single nucleotide variant
Location: chr14:92142302 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 6 PDB
Residue 267: a β-strand

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

Similar variants

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
CPSF2 p.Arg751His 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-ala267val (accessed [today's date]).

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