Is CPSF2 p.Arg579= (c.1737C>T) pathogenic?

CPSF2 p.Arg579= (c.1737C>T) is classified Likely benign in CPSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Low-frequency (popmax 1.22%, mid).

How common is CPSF2 p.Arg579= (c.1737C>T) in the general population?

CPSF2 p.Arg579= (c.1737C>T) is low-frequency (popmax 1.22%, mid) (gnomAD).

CPSF2 p.Arg579=

c.1737C>T · VCV3777798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4.8
Overall
CADD	6.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% Middle Eastern · 74/6,062 alleles

Filtering AF 0.997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.915%

Overall 0.387% 6,239/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.97%	51
Middle Easterngrpmax	1.22%	82
European (non-Finnish)	0.477%	210
Ashkenazi Jewishnot grpmax-eligible	0.324%	308
Remaining individualsnot grpmax-eligible	0.256%	391
Finnishnot grpmax-eligible	0.109%	915
South Asian	0.0867%	1,153
Admixed American	0.0833%	1,200
African / African-American	0.0813%	1,230
East Asian	0.0134%	7,480

Amish 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: CPSF2
Protein: p.Arg579=
Coding: c.1737C>T
MANE Select: NM_017437
Type: single nucleotide variant
Location: chr14:92157800 (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.Arg579His Uncertain significance ★ ⚠ same residue
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.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-arg579 (accessed [today's date]).

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