Is CSTF2T p.Ser3Arg (c.7A>C) pathogenic?

CSTF2T p.Ser3Arg (c.7A>C) is classified Uncertain significance in CSTF2T (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.8891); Very rare (popmax 0.00272%, nfe).

How common is CSTF2T p.Ser3Arg (c.7A>C) in the general population?

CSTF2T p.Ser3Arg (c.7A>C) is very rare (popmax 0.00272%, nfe) (gnomAD).

What do computational predictors say about CSTF2T p.Ser3Arg (c.7A>C)?

AlphaMissense predicts likely pathogenic (score 0.8891) — an in-silico prediction, not a clinical call.

CSTF2T p.Ser3Arg

c.7A>C · VCV4235367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00272%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.8891	likely pathogenic
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP -1.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 314 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	22.8	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 0.00272% European (non-Finnish) · 32/1,177,140 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00205% 33/1,608,288 alleles · very rare exomes 32/1,456,368 · genomes 1/151,920 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00272%	36,786
Remaining individualsnot grpmax-eligible	0.00161%	62,244

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.Ser3Arg
Coding: c.7A>C
MANE Select: NM_015235
Type: single nucleotide variant
Location: chr10:51699543 (GRCh38)

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

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-ser3arg (accessed [today's date]).

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