Is CSTF2T p.Val177Ile (c.529G>A) pathogenic?

CSTF2T p.Val177Ile (c.529G>A) is classified Uncertain significance in CSTF2T (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: ambiguous (0.5072); Very rare (popmax 0.000169%, nfe).

How common is CSTF2T p.Val177Ile (c.529G>A) in the general population?

CSTF2T p.Val177Ile (c.529G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CSTF2T p.Val177Ile (c.529G>A)?

AlphaMissense predicts ambiguous (score 0.5072) — an in-silico prediction, not a clinical call.

CSTF2T p.Val177Ile

c.529G>A · VCV3269973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5072	ambiguous
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 810 bp · p 0.42 · regional, not allelic
Overall
CADD	24.7	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 0.000169% European (non-Finnish) · 2/1,180,058 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,138 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: CSTF2T
Protein: p.Val177Ile
Coding: c.529G>A
MANE Select: NM_015235
Type: single nucleotide variant
Location: chr10:51699021 (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-val177ile (accessed [today's date]).

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