Is CSTF1 p.Asp290Asn (c.868G>A) pathogenic?

CSTF1 p.Asp290Asn (c.868G>A) is classified Uncertain significance in CSTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). AlphaMissense: likely pathogenic (0.9391); Absent from gnomAD v4.1.

How common is CSTF1 p.Asp290Asn (c.868G>A) in the general population?

CSTF1 p.Asp290Asn (c.868G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSTF1 p.Asp290Asn (c.868G>A)?

AlphaMissense predicts likely pathogenic (score 0.9391) — an in-silico prediction, not a clinical call.

CSTF1 p.Asp290Asn

c.868G>A · rs2515876531 · VCV2237726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9391 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9391	likely pathogenic
REVEL	0.552	indeterminate
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 6,009 bp · p 1.5e-21 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSTF1
Protein: p.Asp290Asn
Coding: c.868G>A
MANE Select: NM_001324
dbSNP: rs2515876531
Type: single nucleotide variant
Location: chr20:56399189 (GRCh38)
Gene constraint: LOEUF 0.116 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.65 · 2 PDB
Residue 290: a β-strand

Full CSTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTF1 p.Ala68Val Uncertain significance ★ ⚠ same type
CSTF1 p.Arg11His Uncertain significance ★ ⚠ same type
CSTF1 p.Arg221Cys Uncertain significance ★ ⚠ same type
CSTF1 p.Arg339Gln Uncertain significance ★ ⚠ same type
CSTF1 p.Arg401Cys Uncertain significance ★ ⚠ same type
CSTF1 p.Arg71His Uncertain significance ★ ⚠ same type
CSTF1 p.Asn32Ser Uncertain significance ★ ⚠ same type
CSTF1 p.Asn36Ser 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/cstf1-p-asp290asn (accessed [today's date]).

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