Is CSTF2T p.Cys441Ser (c.1322G>C) pathogenic?

CSTF2T p.Cys441Ser (c.1322G>C) is classified Uncertain significance in CSTF2T (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1764); Rare (popmax 0.118%, eas).

How common is CSTF2T p.Cys441Ser (c.1322G>C) in the general population?

CSTF2T p.Cys441Ser (c.1322G>C) is rare (popmax 0.118%, eas) (gnomAD).

What do computational predictors say about CSTF2T p.Cys441Ser (c.1322G>C)?

AlphaMissense predicts likely benign (score 0.1764) — an in-silico prediction, not a clinical call.

CSTF2T p.Cys441Ser

c.1322G>C · rs759490518 · VCV3078443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1764	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -4.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 665 bp · p 0.67 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,868 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.00935% 151/1,614,194 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	847
South Asian	0.0867%	1,153
Remaining individualsnot grpmax-eligible	0.0048%	20,835
African / African-American	0.00133%	75,054
European (non-Finnish)	0.00127%	78,669

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.Cys441Ser
Coding: c.1322G>C
MANE Select: NM_015235
dbSNP: rs759490518
Type: single nucleotide variant
Location: chr10:51698228 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 60.27
Residue 441: the '9 x 5 aa tandem repeats of m-e-t-r-[ag]' 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.Arg302Trp 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

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-cys441ser (accessed [today's date]).

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