Is CPSF2 p.Asp773His (c.2317G>C) pathogenic?

CPSF2 p.Asp773His (c.2317G>C) is classified Uncertain significance in CPSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: ambiguous (0.3735); Very rare (popmax 0.00229%, eas).

How common is CPSF2 p.Asp773His (c.2317G>C) in the general population?

CPSF2 p.Asp773His (c.2317G>C) is very rare (popmax 0.00229%, eas) (gnomAD).

What do computational predictors say about CPSF2 p.Asp773His (c.2317G>C)?

AlphaMissense predicts ambiguous (score 0.3735) — an in-silico prediction, not a clinical call.

CPSF2 p.Asp773His

c.2317G>C · rs2545247603 · VCV3076884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3735	ambiguous
REVEL	0.255	benign-leaning
SaProt	LLR -10.03	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 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 19 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	27.9	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 0.00229% East Asian · 1/43,592 alleles

Overall 6.94e-05% 1/1,441,416 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: CPSF2
Protein: p.Asp773His
Coding: c.2317G>C
MANE Select: NM_017437
dbSNP: rs2545247603
Type: single nucleotide variant
Location: chr14:92161712 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 6 PDB

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-asp773his (accessed [today's date]).

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