Is CSTF2T p.Met144Val (c.430A>G) pathogenic?

CSTF2T p.Met144Val (c.430A>G) is classified Uncertain significance in CSTF2T (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9596); Ultra-rare (popmax 0.0317%, amr).

How common is CSTF2T p.Met144Val (c.430A>G) in the general population?

CSTF2T p.Met144Val (c.430A>G) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CSTF2T p.Met144Val (c.430A>G)?

AlphaMissense predicts likely pathogenic (score 0.9596) — an in-silico prediction, not a clinical call.

CSTF2T p.Met144Val

c.430A>G · VCV4657349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9596 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9596	likely pathogenic
REVEL	0.265	benign-leaning
SaProt	LLR -13.21	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 810 bp · p 0.42 · regional, not allelic
Overall
CADD	24.5	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 0.0317% Admixed American · 19/60,012 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00192% 31/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,159
East Asian	0.0245%	4,081
European (non-Finnish)	8.47e-05%	1,180,050

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.Met144Val
Coding: c.430A>G
MANE Select: NM_015235
Type: single nucleotide variant
Location: chr10:51699120 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 60.27

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-met144val (accessed [today's date]).

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