Is CSTF2 p.Pro9Ser (c.25C>T) pathogenic?

CSTF2 p.Pro9Ser (c.25C>T) is classified Uncertain significance in CSTF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). AlphaMissense: ambiguous (0.5027); Very rare (popmax 0.00348%, afr).

How common is CSTF2 p.Pro9Ser (c.25C>T) in the general population?

CSTF2 p.Pro9Ser (c.25C>T) is very rare (popmax 0.00348%, afr) (gnomAD).

What do computational predictors say about CSTF2 p.Pro9Ser (c.25C>T)?

AlphaMissense predicts ambiguous (score 0.5027) — an in-silico prediction, not a clinical call.

CSTF2 p.Pro9Ser

c.25C>T · rs1242418398 · VCV2549382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5027 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, afr)

Computational evidence

Protein change
AlphaMissense	0.5027	ambiguous
REVEL	0.304	indeterminate
SaProt	LLR -8.37	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 3,712 bp · p 3.2e-17 · regional, not allelic
Overall
CADD	24.1	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 0.00348% African / African-American · 2/57,424 alleles

Filtering AF 0.000578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.00107% 13/1,210,643 alleles · very rare exomes 12/1,097,987 · genomes 1/112,656 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00348%	28,712
Remaining individualsnot grpmax-eligible	0.0021%	47,594
European (non-Finnish)	0.00112%	89,513

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: CSTF2
Protein: p.Pro9Ser
Coding: c.25C>T
MANE Select: NM_001325
dbSNP: rs1242418398
Type: single nucleotide variant
Location: chrX:100820441 (GRCh38)
Structure: AlphaFold pLDDT 60.94 · 4 PDB

Full CSTF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTF2 p.Pro380= Benign ★★ same type
CSTF2 c.1031+3A>C Uncertain significance ★ same type
CSTF2 p.Ala108Val Uncertain significance ★ ⚠ same type
CSTF2 p.Ala242Val Uncertain significance ★ ⚠ same type
CSTF2 p.Ala263Thr Uncertain significance ★ ⚠ same type
CSTF2 p.Ala427Val Uncertain significance ★ ⚠ same type
CSTF2 p.Arg294Gln Uncertain significance ★ ⚠ same type
CSTF2 p.Arg330Gln 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/cstf2-p-pro9ser (accessed [today's date]).

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