Is ERG p.Asp40Asn (c.118G>A) pathogenic?

ERG p.Asp40Asn (c.118G>A) is classified Uncertain significance in ERG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.1231); Very rare (popmax 0.004%, afr).

How common is ERG p.Asp40Asn (c.118G>A) in the general population?

ERG p.Asp40Asn (c.118G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ERG p.Asp40Asn (c.118G>A)?

AlphaMissense predicts likely benign (score 0.1231) — an in-silico prediction, not a clinical call.

ERG p.Asp40Asn

c.118G>A · rs769957252 · VCV2236261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1231	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 96 kb · p 0.0017 · regional, not allelic
Overall
CADD	24.5	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 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00105% 17/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,969
East Asian	0.00223%	44,870
European (non-Finnish)	0.0011%	90,770

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.Asp40Asn
Coding: c.118G>A
MANE Select: NM_182918
dbSNP: rs769957252
Type: single nucleotide variant
Location: chr21:38445522 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.25 · 8 PDB
Residue 40: the 'disordered' region

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-asp40asn (accessed [today's date]).

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