Is ERG p.Gln161Glu (c.481C>G) pathogenic?

ERG p.Gln161Glu (c.481C>G) is classified Uncertain significance in ERG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0795); Ultra-rare (popmax 0.0233%, amr).

How common is ERG p.Gln161Glu (c.481C>G) in the general population?

ERG p.Gln161Glu (c.481C>G) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about ERG p.Gln161Glu (c.481C>G)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

ERG p.Gln161Glu

c.481C>G · rs1422456446 · VCV2393893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 96 kb · p 0.0017 · regional, not allelic
Overall
CADD	24.9	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 0.0233% Admixed American · 14/60,010 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.000991% 16/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: ERG
Protein: p.Gln161Glu
Coding: c.481C>G
MANE Select: NM_182918
dbSNP: rs1422456446
Type: single nucleotide variant
Location: chr21:38403617 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.25 · 8 PDB
Residue 161: the pnt domain

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-gln161glu (accessed [today's date]).

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