Is ERG p.Pro116Arg (c.347C>G) pathogenic?

ERG p.Pro116Arg (c.347C>G) is classified Uncertain significance in ERG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.3293); Very rare (popmax 0.00551%, nfe).

How common is ERG p.Pro116Arg (c.347C>G) in the general population?

ERG p.Pro116Arg (c.347C>G) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about ERG p.Pro116Arg (c.347C>G)?

AlphaMissense predicts likely benign (score 0.3293) — an in-silico prediction, not a clinical call.

ERG p.Pro116Arg

c.347C>G · rs760655364 · VCV3090150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3293	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 96 kb · p 0.0017 · regional, not allelic
Overall
CADD	25.2	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 0.00551% European (non-Finnish) · 65/1,179,976 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00428% 69/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,153
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,461

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.Pro116Arg
Coding: c.347C>G
MANE Select: NM_182918
dbSNP: rs760655364
Type: single nucleotide variant
Location: chr21:38423451 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.25 · 8 PDB
Residue 116: the pnt domain; an α-helix

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-pro116arg (accessed [today's date]).

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