Is CSTF2T p.Arg302Trp (c.904C>T) pathogenic?

CSTF2T p.Arg302Trp (c.904C>T) is classified Uncertain significance in CSTF2T (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-16). AlphaMissense: ambiguous (0.4906); Very rare (popmax 0.00659%, sas).

How common is CSTF2T p.Arg302Trp (c.904C>T) in the general population?

CSTF2T p.Arg302Trp (c.904C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CSTF2T p.Arg302Trp (c.904C>T)?

AlphaMissense predicts ambiguous (score 0.4906) — an in-silico prediction, not a clinical call.

CSTF2T p.Arg302Trp

c.904C>T · rs778762664 · VCV2394939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4906	ambiguous
REVEL	0.159	moderately benign-leaning
SaProt	LLR -10.95	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 810 bp · p 0.42 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00659% South Asian · 6/91,088 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000682% 11/1,613,948 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
East Asian	0.00446%	22,441
African / African-American	0.00133%	74,914
European (non-Finnish)	0.000169%	590,019

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: CSTF2T
Protein: p.Arg302Trp
Coding: c.904C>T
MANE Select: NM_015235
dbSNP: rs778762664
Type: single nucleotide variant
Location: chr10:51698646 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 60.27
Residue 302: the 'disordered' region

Full CSTF2T gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTF2T p.Ala158Thr Uncertain significance ★ ⚠ same type
CSTF2T p.Ala417Val Uncertain significance ★ ⚠ same type
CSTF2T p.Ala5Val Uncertain significance ★ ⚠ same type
CSTF2T p.Ala615Val Uncertain significance ★ ⚠ same type
CSTF2T p.Arg373Cys Uncertain significance ★ ⚠ same type
CSTF2T p.Arg373His Uncertain significance ★ ⚠ same type
CSTF2T p.Arg373Ser Uncertain significance ★ ⚠ same type
CSTF2T p.Arg413Gly 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/cstf2t-p-arg302trp (accessed [today's date]).

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