Is ERG p.Thr120Lys (c.359C>A) pathogenic?

ERG p.Thr120Lys (c.359C>A) is classified Uncertain significance in ERG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: ambiguous (0.4312); Absent from gnomAD v4.1.

How common is ERG p.Thr120Lys (c.359C>A) in the general population?

ERG p.Thr120Lys (c.359C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERG p.Thr120Lys (c.359C>A)?

AlphaMissense predicts ambiguous (score 0.4312) — an in-silico prediction, not a clinical call.

ERG p.Thr120Lys

c.359C>A · rs772248149 · VCV2605996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4312 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4312	ambiguous
REVEL	0.21	benign-leaning
SaProt	LLR -6.07	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 9.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 96 kb · p 0.0017 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERG
Protein: p.Thr120Lys
Coding: c.359C>A
MANE Select: NM_182918
dbSNP: rs772248149
Type: single nucleotide variant
Location: chr21:38423439 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.25 · 8 PDB
Residue 120: the pnt domain; a turn

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

Similar variants

ERG p.Asp363Gly Uncertain significance ★★ ⚠ same type
ERG c.389-2A>G Uncertain significance ★ same type
ERG c.40-56923A>G Uncertain significance ★ same type
ERG c.674-1G>A Uncertain significance ★ same type
ERG p.Ala368Thr Uncertain significance ★ ⚠ same type
ERG p.Ala387Pro Uncertain significance ★ ⚠ same type
ERG p.Ala88Asp Uncertain significance ★ ⚠ same type
ERG p.Arg178Gly 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/erg-p-thr120lys (accessed [today's date]).

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