Is CSTF3 p.Pro477Arg (c.1430C>G) pathogenic?

CSTF3 p.Pro477Arg (c.1430C>G) is classified Uncertain significance in CSTF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.3394); Very rare (popmax 8.51e-05%, nfe).

How common is CSTF3 p.Pro477Arg (c.1430C>G) in the general population?

CSTF3 p.Pro477Arg (c.1430C>G) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about CSTF3 p.Pro477Arg (c.1430C>G)?

AlphaMissense predicts likely benign (score 0.3394) — an in-silico prediction, not a clinical call.

CSTF3 p.Pro477Arg

c.1430C>G · VCV4007782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3394	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 20 kb · p 1e-53 · regional, not allelic
Overall
CADD	29.7	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 8.51e-05% European (non-Finnish) · 1/1,174,716 alleles

Overall 0.000657% 1/152,164 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: CSTF3
Protein: p.Pro477Arg
Coding: c.1430C>G
MANE Select: NM_001326
Type: single nucleotide variant
Location: chr11:33092286 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.85 · 3 PDB

Full CSTF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTF3 c.1272+2T>C Uncertain significance ★ same type
CSTF3 p.Ala59Val Uncertain significance ★ ⚠ same type
CSTF3 p.Arg51Trp Uncertain significance ★ ⚠ same type
CSTF3 p.Arg551Pro Uncertain significance ★ ⚠ same type
CSTF3 p.Arg644Gln Uncertain significance ★ ⚠ same type
CSTF3 p.Asn148Ser Uncertain significance ★ ⚠ same type
CSTF3 p.Asp404Tyr Uncertain significance ★ ⚠ same type
CSTF3 p.Cys628Tyr 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/cstf3-p-pro477arg (accessed [today's date]).

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