Is CPSF1 p.Thr1173= (c.3519C>T) pathogenic?

CPSF1 p.Thr1173= (c.3519C>T) is classified Likely benign in CPSF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-14). Rare (popmax 0.304%, nfe).

How common is CPSF1 p.Thr1173= (c.3519C>T) in the general population?

CPSF1 p.Thr1173= (c.3519C>T) is rare (popmax 0.304%, nfe) (gnomAD).

CPSF1 p.Thr1173=

c.3519C>T · rs140031041 · VCV3035139

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.304%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.5
Overall
CADD	0.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.304% European (non-Finnish) · 3,584/1,179,596 alleles

Filtering AF 0.296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.292%

Overall 0.278% 4,487/1,612,498 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.43%	233
Ashkenazi Jewishnot grpmax-eligible	0.352%	284
European (non-Finnish)grpmax	0.304%	329
Remaining individualsnot grpmax-eligible	0.231%	434
South Asian	0.207%	484
Middle Eastern	0.198%	505
Admixed American	0.175%	570
African / African-American	0.0946%	1,057
East Asian	0.0156%	6,406

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: CPSF1
Protein: p.Thr1173=
Coding: c.3519C>T
MANE Select: NM_013291
dbSNP: rs140031041
Type: single nucleotide variant
Location: chr8:144394692 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.97 · 13 PDB
Residue 1173: a UniProt-annotated variant site (in myp27); a β-strand

Full CPSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF1 p.Ala1319Thr Uncertain significance ★★ ⚠ same type
CPSF1 p.Thr561Ile Uncertain significance ★★ ⚠ same type
CPSF1 p.Gly722= Likely benign ★★ same type
CPSF1 p.Leu1360= Likely benign ★★ same type
CPSF1 p.Pro438= Likely benign ★★ same type
CPSF1 p.Pro654= Likely benign ★★ same type
CPSF1 c.539+1G>A Likely pathogenic ★ same type
CPSF1 c.1119+2T>G 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/cpsf1-p-thr1173 (accessed [today's date]).

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